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Gene:
CYP2C9
cytochrome P450, family 2, subfamily C, polypeptide 9

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Dosing Guidelines Drug Labels Clinical Annotations Genetic Tests

Guidelines regarding the use of pharmacogenomic tests in dosing for warfarin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing.
Julie A. Johnson, Li Gong, Michelle Whirl-Carrillo, Brian F. Gage, Stuart A. Scott, C., Michael Stein, Jeffrey L. Anderson, Stephen E. Kimmel, Ming Ta Michael Lee, Munir Pirmohamed, Mia Wadelius, Teri E. Klein, and Russ B. Altman. Clinical Pharmacology & Therapeutics (2011) Oct;90(4):625-629.

Download: article and supplement

Pharmacogenetic algorithm-based warfarin dosing

Excerpt from the warfarin dosing guidelines:

Numerous studies have derived warfarin dosing algorithms that use both genetic and non-genetic factors to predict warfarin dose [Article:18305455, 19228618, 18574025]. Two algorithms perform well in estimating stable warfarin dose across different ethnic populations; [Article:18305455, 19228618] these were created using more than 5,000 subjects. Dosing algorithms using genetics outperform nongenetic clinical algorithms and fixed-dose approaches in dose prediction [Article:18305455, 19228618].

The best way to estimate the anticipated stable dose of warfarin is to use the algorithms available on http://www.warfarindosing.org (offering both high-performing algorithms [Article:18305455, 19228618]). The dosing algorithm published by the International Warfarin Pharmacogenetics Consortium is also online, at http://www.pharmgkb.org/do/serve?objId=PA162372936&objCls=Dataset#tabview=tab2. The two algorithms provide very similar dose recommendations.

Download: IWPC Pharmacogenetic Dosing Algorithm

Approach to pharmacogenetic-based warfarin dosing without access to dosing algorithms

Excerpt from the warfarin dosing guidelines:

In 2007, the FDA modified the warfarin label, stating that CYP2C9 and VKORC1 genotypes may be useful in determining the optimal initial dose of warfarin [Article:17906972]. The label was further updated in 2010 to include a table (Table 1) describing recommendations for initial dosing ranges for patients with different combinations of CYP2C9 and VKORC1 genotypes.

Genetics-based algorithms also better predict warfarin dose than the FDA-approved warfarin label table [Article:21272753]. Therefore, the use of pharmacogenetic algorithm-based dosing is recommended when possible, although if electronic means for such dosing are not available, the table-based dosing approaches (Table 1) are suggested. The range of doses by VKORC1 genotype and the range of dose recommendations/predictions by the FDA table and algorithm are shown in Figure 2.

Figure 2 Legend: Frequency histograms of stable therapeutic warfarin doses in mg/week, stratified by VKORC1 -1639G>A genotype in 3,616 patients recruited by the International Warfarin Pharmacogenetics Consortium (IWPC) who did not carry the CYP2C9*2 or *3 allele (i.e., coded as *1*1 for US Food and Drug Administration (FDA) table and algorithm dosing). The range of doses within each genotype group recommended on the FDA table is shown via the shaded rectangle. The range of doses predicted using the IWPC dosing algorithm in these 3,616 patients is shown by the solid lines.

Figure 2 demonstrates that the range of individuals covered by the FDA table is much narrower than that of the algorithm. The article and supplement detail important variables that are not covered by the table that should also be taken into consideration.

Table 1: Recommended daily warfarin doses (mg/day) to achieve a therapeutic INR based on CYP2C9 and VKORC1 genotype using the warfarin product insert approved by the United States Food and Drug Administration:

VKORC1 Genotype (-1639G>A, rs9923231)	CYP2C91/1	CYP2C91/2	CYP2C91/3	CYP2C92/2	CYP2C92/3	CYP2C93/3
GG	5-7	5-7	3-4	3-4	3-4	0.5-2
GA	5-7	3-4	3-4	3-4	0.5-2	0.5-2
AA	3-4	3-4	0.5-2	0.5-2	0.5-2	0.5-2

Reproduced from updated warfarin (Coumadin®) product label.

Supplemental Table S1. Genotypes that constitute the * alleles for CYP2C9

Allele	Constituted by genotypes at:	Amino acid changes	Enzymatic Activity
*1	reference allele at all positions		Normal
*2	C>T at rs1799853	R144C	Decreased
*3	A>C at rs1057910	I359L	Decreased

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for acenocoumarol based on CYP2C9 genotype (PMID:21412232).

Genotype	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
CYP2C9 1/2	Check INR more frequently after initiating or discontinuing NSAIDs	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 2/2	Check INR more frequently after initiating or discontinuing NSAIDs	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 1/3	Check INR more frequently after initiating or discontinuing NSAIDs	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x10{^}9^/l; leucopenia > 3.0x10{^}9^/l; thrombocytopenia > 75x10{^}9^/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
CYP2C9 2/3	Check INR more frequently after initiating or discontinuing NSAIDs	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 3/3	Check INR more frequently during dose titration and after initiating or discontinuing NSAIDs	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)

*See Methods or PMID: 18253145 for definition of "good quality."
S: statistically significant difference.
Please see attached PDF for detailed information about the evaluated studies: Acenocoumarol CYP2C9

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for glibenclamide based on CYP2C9 genotype (PMID:21412232). They conclude that there are no recommendations at this time.

Genotype	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
CYP2C9 1/2	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 2/2	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 1/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
CYP2C9 2/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 3/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5

*See Methods or PMID: 18253145 for definition of "moderate" quality.
S: statistically significant difference.

Genotype	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
CYP2C9 1/2	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 2/2	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 1/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 2/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 3/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)

*See Methods or PMID: 18253145 for definition of "moderate" quality.
S: statistically significant difference.
NS: non-significant

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for glimepiride based on CYP2C9 genotype (PMID:21412232). They conclude that there are no recommendations at this time.

Genotype	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
CYP2C9 1/2	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 2/2	None	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 1/3	None	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS)
CYP2C9 2/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea
CYP2C9 3/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea

*See Methods or PMID: 18253145 for definition of "good" and "moderate" quality.
S: statistically significant difference.

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for phenprocoumon based on CYP2C9 genotype (PMID:21412232).

Genotype	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
CYP2C9 1/2	None	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): death; arrhythmia; unanticipated myelosuppression
CYP2C9 2/2	Check INR more frequently	Published controlled studies of good quality\* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): death; arrhythmia; unanticipated myelosuppression
CYP2C9 1/3	None	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): death; arrhythmia; unanticipated myelosuppression
CYP2C9 2/3	Check INR more frequently	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): death; arrhythmia; unanticipated myelosuppression
CYP2C9 3/3	Check INR more frequently	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x10{^}9^/l; leucopenia 1.0-2.0x10{^}9^/l; thrombocytopenia 25-50x10{^}9^/l; severe diarrhea

*See Methods or PMID: 18253145 for definition of "good quality."
S: statistically significant difference.

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for phenytoin based on CYP2C9 genotype (PMID:21412232).

Genotype	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
CYP2C9 1/2	Standard loading dose. Reduce maintenance dose by 25%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation)	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 2/2	Standard loading dose. Reduce maintenance dose by 50%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation)	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 1/3	Standard loading dose. Reduce maintenance dose by 25%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation)	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x10{^}9^/l; leucopenia 1.0-2.0x10{^}9^/l; thrombocytopenia 25-50x10{^}9^/l; severe diarrhea
CYP2C9 2/3	Standard loading dose. Reduce maintenance dose by 50%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation)	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 3/3	Standard loading dose. Reduce maintenance dose by 50%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation)	Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x10{^}9^/l; leucopenia 1.0-2.0x10{^}9^/l; thrombocytopenia 25-50x10{^}9^/l; severe diarrhea

*See Methods or PMID: 18253145 for definition of "good quality."
S: statistically significant difference.

The Royal Dutch Association for the Advancement of Pharmacy - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for tolbutamide based on CYP2C9 genotype (PMID:21412232).They conclude that there are no recommendations at this time.

Genotype	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
CYP2C9 1/2	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 2/2	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 1/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
CYP2C9 2/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (NS) Kinetic effect (NS)
CYP2C9 3/3	None	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5

*See Methods or PMID: 18253145 for definition of "moderate" quality.
S: statistically significant difference.

Information regarding PGx on FDA drug labels is derived from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels". Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

The FDA recommends, but does not require, genetic testing of patients from at-risk populations prior to initiating treatment with CELEBREX.

Excerpt from the CELEBREX drug label:

"Poor Metabolizers of CYP2C9 Substrates: Patients who are known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin) should be administered celecoxib with caution. Consider starting treatment at half the lowest recommended dose in poor metabolizers. Consider using alternative management in JRA patients who are poor metabolizers..."

"Celecoxib metabolism is primarily mediated via CYP2C9...CYP2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C9*2 and CYP2C9*3 polymorphisms. Limited data from 4 published reports that included a total of 8 subjects with the homozygous CYP2C9*3/*3 genotype showed celecoxib systemic levels that were 3- to 7-fold higher in these subjects compared to subjects with CYP2C9*1/*1 or *I/*3 genotypes. The pharmacokinetics of celecoxib have not been evaluated in subjects with other CYP2C9 polymorphisms, such as *2, *5, *6, *9 and *11. It is estimated that the frequency of the homozygous *3/*3 genotype is 0.3% to 1.0% in various ethnic groups."

"Consider a dose reduction by 50% (or alternative management for JRA) in patients who are known or suspected to be CYP2C9 poor metabolizers."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Celecoxib drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Flurbiprofen.

PGx information can be found in the Clinical Pharmacology and Special Populations label sections.

Excerpts from the Flurbiprofen label:

In vitro studies have
demonstrated that cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4'-hydroxyflurbiprofen.

Aspirin: Concurrent administration of Flurbiprofen tablet, USP and aspirin resulted in 50% lower serum flurbiprofen concentrations.
This effect of aspirin (which is also seen with other nonsteroidal anti-inflammatory drugs) has been demonstrated in patients with
rheumatoid arthritis (n=15) and in healthy volunteers (n=16)

The effect of flurbiprofen on blood pressure response to propranolol and atenolol was evaluated
in men with mild uncomplicated hypertension (n=10). Flurbiprofen pretreatment attenuated the hypotensive effect of a single dose of
propranolol but not atenolol.

Studies in healthy volunteers have shown that, like other nonsteroidal anti-inflammatory drugs, flurbiprofen can interfere
with the effects of furosemide. Although results have varied from study to study, effects have been shown on furosemide-stimulated
diuresis, natriuresis, and kaliuresis. Other nonsteroidal anti-inflammatory drugs that inhibit prostaglandin synthesis have been shown
to interfere with thiazide and potassium-sparing diuretics

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the flurbiprofen drug label.

The FDA recommends genetic testing prior to initiating treatment with warfarin.

Excerpt from the warfarin drug label:

The patient's CYP2C9 and VKORC1 genotype information, when available, can assist in selection of the starting dose. Table 5 describes the range of stable maintenance doses observed in multiple patients having different combinations of CYP2C9 and VKORC1 gene variants. Consider these ranges in choosing the initial dose.

The VKORC1:G-1639A polymorphism is associated with lower dose requirements for warfarin in Caucasian and Asian patients. Increased bleeding risk and lower initial warfarin dose requirements have been associated with the CYP2C9*2 and CYP2C9*3 alleles. Approximately 30% of the variance in warfarin dose could be attributed to genetic variation in VKORC1, and about 40% of dose variance could be explained taking into consideration both VKORC1 and CYP2C9 genetic polymorphisms. Accounting for genetic variation in both VKORC1 and CYP2C9, age, height, body weight, interacting drugs, and indication for warfarin therapy explained about 55% of the variability in warfarin dose.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the warfarin drug label. Pharmacogenomics-related dosing information is found in Table 5 on page 27.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Fluvoxamine.

PGx information can be found in the Drug Interactions label section.

Excerpts from the fluvoxamine label:

Based on a finding of substantial interactions of fluvoxamine with certain of these drugs (see later parts of this section and also WARNINGS for details) and limited in vitro data for the 3A4 isozyme, it appears that fluvoxamine inhibits the following isozymes
that are known to be involved in the metabolism of the listed drugs:
1A2, 2C9, 3A4, 2C19, Warfarin, Alprazolam, Omeprazole, Theophylline, Propranolol, Tizanidine. In vitro data suggest that fluvoxamine is a relatively weak inhibitor of the 2D6 isozyme.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the fluvoxamine drug label.

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below. Please follow the link in the "Position" column for more information about a particular variant. Each link in the "Position" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Position ?	Drug ?	Relevance ?	Strength of Evidence ?
rs1057910	warfarin	To see relevance please register or sign in.	1
rs1799853	warfarin	To see relevance please register or sign in.	2
rs1799853	sulfonamides, urea derivatives	To see relevance please register or sign in.	2
rs7900194	warfarin	To see relevance please register or sign in.	2
rs9332131	warfarin	To see relevance please register or sign in.	2
rs28371685	warfarin	To see relevance please register or sign in.	2
rs1057910	sulfonamides, urea derivatives	To see relevance please register or sign in.	2
rs28371686	warfarin	To see relevance please register or sign in.	2
rs4086116	acenocoumarol	To see relevance please register or sign in.	3
rs1057910	acenocoumarol	To see relevance please register or sign in.	3

Download a summary of all Clinical Annotations available.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

A non-comprehensive list of genetic tests for specific variants, including descriptions of and links to individual tests; manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

PGx Test	Variants Assayed	Related Drugs?
TrimGen Corporation eQ-PCR LC Warfarin Genotyping Kit	CYP2C92, CYP2C93	warfarin

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

view legend

	Variant? (build 132)	Alternate Names ?	Drugs ?	Alleles ? (+ chr strand)	Function ?	Amino Acid? Translation
VIP CA VA	rs1057910	CYP2C93, CYP2C93:Ile359Leu, CYP2C9: I359L, CYP2C9:359Ile>Leu, CYP2C9:Ile359Leu, c.1075A>C, g.47545517A>C, g.47639A>C, g.96731043A>C, mRNA 11A>C, p.Ile359Leu	acenocoumarol celecoxib Antiinflammatory agents, non-steroids losartan glimepiride warfarin gliclazide naproxen ibuprofen phenprocoumon phenytoin sulfonamides, urea derivatives valproic acid diclofenac tolbutamide glibenclamide piroxicam	A > T A > C A > G	Missense	Ile359Leu
VA	rs12782374		warfarin phenytoin	G > A	Not Available
VIP CA VA	rs1799853	CYP2C9*2, CYP2C9:144Arg>Cys, CYP2C9:Arg144Cys, c.430C>T, g.47506511C>T, g.8633C>T, g.96692037C>T, mRNA 455C>T, p.Arg144Cys	acenocoumarol celecoxib sulfonamides, urea derivatives valproic acid tolbutamide glimepiride gliclazide warfarin phenprocoumon phenytoin glibenclamide	C > G C > T C > A	Missense	Arg144Cys
CA VA	rs28371685	CYP2C9*11, CYP2C9:R335W, c.1003C>T, g.47545445C>T, g.47567C>T, p.Arg335Trp	warfarin phenytoin	C > T	Missense	Arg335Trp
CA VA	rs28371686	CYP2C9*5, CYP2C9:D360E, c.1080C>G, g.47545522C>G, p.Asp360Glu	warfarin phenytoin	C > G	Missense	Asp360Glu
CA VA	rs4086116	c.482-334C>T, g.13788C>T, g.47511666C>T	acenocoumarol phenprocoumon	C > T	Intronic
VA	rs7089580		warfarin	A > T	Intronic
VA	rs71486745		warfarin phenytoin	GT > -	Not Available
VA	rs72558187		warfarin	T > C	Not Available	Leu90Pro
CA VA	rs7900194	CYP2C9*8, CYP2C9:R150H, c.449G>A, g.47506530G>A, g.8652G>A, p.Arg150His	warfarin phenytoin	G > A	Missense	Arg150His
VA	rs9332127		warfarin	G > C	Intronic
CA VA	rs9332131	CYP2C9*6, CYP2C9:null allele, c.817delA, g.15625delA, g.47513503delA, p.Lys273fx	warfarin phenytoin	A > -	Frameshift
VA	rs9332239	c.1465C>T, g.47553241C>T, g.55363C>T, p.Pro489Ser	tolbutamide	C > T	Missense	Pro489Ser

Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP build 132

Overview

Alternate Names:	OTTHUMP00000020135; cytochrome P-450 S-mephenytoin 4-hydroxylase; cytochrome P-450MP; cytochrome P450 2C9; cytochrome P450 PB-1; cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 10; cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 9; cytochrome p4502C9; flavoprotein-linked monooxygenase; mephenytoin 4-hydroxylase; microsomal monooxygenase; xenobiotic monooxygenase
Alternate Symbols:	CPC9; CYP2C; CYP2C10; CYP2C91; CYP2C91A; CYPIIC9; MGC149605; MGC88320; P450 MP-4; P450 PB-1; P450IIC9
Haplotypes:	CYP2C91; CYP2C92; CYP2C93; CYP2C94; CYP2C95; CYP2C96; CYP2C97; CYP2C98; CYP2C99; CYP2C910; CYP2C911; CYP2C912; CYP2C913; CYP2C914; CYP2C915; CYP2C916; CYP2C917; CYP2C918; CYP2C919; CYP2C920; CYP2C921; CYP2C922; CYP2C923; CYP2C924; CYP2C925; CYP2C926; CYP2C927; CYP2C928; CYP2C929; CYP2C930; CYP2C931; CYP2C932; CYP2C933; CYP2C934
PharmGKB Accession Id:	PA126

Details

Cytogenetic Location:	chr10 : q23.33 - q23.33
GP mRNA Boundary†:	chr10 : 96698415 - 96749148
GP Gene Boundary†:	chr10 : 96688415 - 96752148
Strand:	plus
Product Name:	No data available

† The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

All alleles are displayed on the positive chromosomal strand.

Download Haplotype Data (CSV)

Haplotype	rs1057910	rs1057911	rs1799853	rs2256871	rs28371685	rs28371686	rs56165452	rs57505750	rs67807361	rs72558184	rs72558187	rs72558188	rs72558189	rs72558190	rs72558192	rs72558193	rs7900194	rs9332130	rs9332131	rs9332239
CYP2C9*1	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*2	A	A	T	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*3	C	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*4	A	A	C	A	C	C	C	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*5	A	A	C	A	C	G	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*6	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	del	C
CYP2C9*7	A	A	C	A	C	C	T	C	A	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*8	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	A	A	A	C
CYP2C9*9	A	A	C	G	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*10	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	G	A	C
CYP2C9*11	A	A	C	A	T	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*12	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	T
CYP2C9*13	A	A	C	A	C	C	T	C	C	G	C	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*14	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	A	C	A	A	G	A	A	C
CYP2C9*15	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	A	A	A	G	A	A	C
CYP2C9*16	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	G	A	G	A	A	C
CYP2C9*17	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*18	C	T	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	C	G	A	A	C
CYP2C9*19	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*20	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*21	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*22	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*23	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*24	A	A	C OR T	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*25	A	A	C	A	C	C	T	C	C	G	T	del	G	C	A	A	G	A	A	C
CYP2C9*26	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*27	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*28	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*29	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*30	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*31	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*32	A	A	C	A	C	C	T	C	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*33	A	A	C	A	C	C	T	C	C	A	T	AGAAATGGAA	G	C	A	A	G	A	A	C
CYP2C9*34	A	A	C	A	C	C	T	T	C	G	T	AGAAATGGAA	G	C	A	A	G	A	A	C

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

Anti-diabetic Drug Nateglinide Pathway, Pharmacokinetics
Nateglinide metabolism and transport in liver cell.

Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics
Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.

Caffeine Pathway, Pharmacokinetics
Stylized liver cell showing candidate genes involved in the metabolism of caffeine.

Celecoxib Pathway, Pharmacokinetics

Clopidogrel Pathway, Pharmacokinetics
Clopidogrel metabolism.

Cyclophosphamide Pathway, Pharmacokinetics
Model human liver cell showing genes involved in the metabolism of cyclophosphamide.

Fluoxetine Pathway, Pharmacokinetics
Representation of the candidate genes involved in the metabolism of fluoxetine.

Fluvastatin Pathway, Pharmacokinetics
Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.

Gefitinib Pathway (PK)
Representation of the candidate genes involved in the transportation and metabolism of gefitinib

Ifosfamide Pathway (PK)
Model human liver cell showing genes involved in the metabolism of ifosfamide

Imatinib Pathway, Pharmacokinetics/Pharmacodynamics

Losartan Pathway, Pharmacokinetics
Representation of the candidate genes involved in the metabolism of losartan.

Nevirapine Pathway, Pharmacokinetics
Representation of candidate genes involved in biotransformation of nevirapine and its mechanism of action in an infected liver cell.

Phenytoin Pathway, Pharmacokinetics
Genes involved in the metabolism of phenytoin in the human liver cell.

Rosiglitazone Pharmacokinetic Pathway
Rosiglitazone is transported from hepatic sinusoids into hepatocytes -- a process mediated by the organic anion transporting polypeptide, where is is metabolized by cytochrome p450 2C8 and 2C9.

Statin Pathway - Generalized, Pharmacokinetics
Representation of the superset of all genes involved in the transport, metabolism and clearance of statin class drugs.

Tamoxifen Pathway, Pharmacokinetics
Tamoxifen metabolism in the liver.

Warfarin Pathway, Pharmacokinetics
Representation of the candidate genes involved in transport, metabolism and clearance of warfarin.

Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics
Representation of candidate genes involved in the metabolism of zidovudine and its mechanism of antiviral action.

External Pathways

Links to non-PharmGKB pathways.

Xenobiotics - (Reactome via Pathway Interaction Database)

Curated Information ?

view legend

Evidence	Gene
DL	CYP1A2
DL	CYP2C19
DL	CYP2D6
DL	CYP3A4
DG DL	VKORC1

Curated Information ?

view legend

Evidence	Drug
DG CA VA	acenocoumarol
PW	atorvastatin
PW	caffeine
VA	carvedilol
DL VA VIP PW	celecoxib
VIP PW	cyclophosphamide
VA VIP	diclofenac
PW	fluoxetine
DL	flurbiprofen
VIP PW	fluvastatin
DL	fluvoxamine
DG VA VIP	glibenclamide
DG VA	gliclazide
DG VA VIP	glimepiride
VIP	glipizide
VA VIP	ibuprofen
PW	imatinib
VIP	irbesartan
VA VIP PW	losartan
PW	lovastatin
VIP	meloxicam
VA VIP	naproxen
PW	nateglinide
PW	nevirapine
DG VA	phenprocoumon
DG VA VIP PW	phenytoin
VA	piroxicam
PW	rosiglitazone
PW	simvastatin
VIP PW	tamoxifen
PW	theophylline
DG VA VIP	tolbutamide
VA	valproic acid
DG DL CA VA VIP PW	warfarin
PW	zidovudine

Evidence	Drug Class
VA	antiepileptics
VA	Antiinflammatory agents, non-steroids
PW	hmg coa reductase inhibitors
CA VA	sulfonamides, urea derivatives

Curated Information ?

view legend

Evidence	Disease
CA VA	Atrial Fibrillation
VA	Coronary Artery Disease
CA VA	Diabetes Mellitus, Type 2
VA	Drug Resistance
VA	Drug Toxicity
VA	Epilepsy
VA	Myocardial Infarction
CA	Pulmonary Embolism
CA	Stroke
CA	Venous Thrombosis

Publications related to CYP2C9: 329

view legend

PW	Celecoxib pathways: pharmacokinetics and pharmacodynamics. Pharmacogenetics and genomics. 2012. Gong Li, et al. [Article:22336956@PubMed]
PW	PharmGKB summary: caffeine pathway. Pharmacogenetics and genomics. 2012. Thorn Caroline F, et al. [Article:22293536@PubMed]
	Genetic polymorphisms are associated with variations in warfarin maintenance dose in Han Chinese patients with venous thromboembolism. Pharmacogenomics. 2012. Zhang Wei, et al. [Article:22248286@PubMed]
	Validation of warfarin pharmacogenetic algorithms in clinical practice. Pharmacogenomics. 2012. Marin-Leblanc Mélina, et al. [Article:22176621@PubMed]
	Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes. The pharmacogenomics journal. 2012. Martis S, et al. [Article:22491019@PubMed]
	Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations. Annals of hematology. 2011. Gan Gin Gin, et al. [Article:21110192@PubMed]
VA	CYP2C9 polymorphism in patients with epilepsy: genotypic frequency analyzes andphenytoin adverse reactions correlation. Arquivos de neuro-psiquiatria. 2011. Twardowschy Carlos Alexandre, et al. [Article:21537551@PubMed]
	Prospective evaluation of a pharmacogenetics-guided warfarin loading and maintenance dose regimen for initiation of therapy. Blood. 2011. Gong Inna Y, et al. [Article:21725053@PubMed]
	The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents. Breast cancer research and treatment. 2011. Lu Wenjie Jessie, et al. [Article:21814747@PubMed]
VA	Extremely low warfarin dose in patients with genotypes of CYP2C93/3 and VKORC1-1639A/A. Chinese medical journal. 2011. Gao Lei, et al. [Article:22040439@PubMed]
	Enantiomers of naringenin as pleiotropic, stereoselective inhibitors of cytochrome P450 isoforms. Chirality. 2011. Lu Wenjie Jessie, et al. [Article:21953762@PubMed]
	Pharmacogenomics: the genetics of variable drug responses. Circulation. 2011. Roden Dan M, et al. [Article:21502584@PubMed]
	Activity Levels of Tamoxifen Metabolites at the Estrogen Receptor and the Impact of Genetic Polymorphisms of Phase I and II Enzymes on Their Concentration Levels in Plasma. Clinical pharmacology and therapeutics. 2011. Mürdter T E, et al. [Article:21451508@PubMed]
	Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing. Clinical pharmacology and therapeutics. 2011. Johnson J A, et al. [Article:21900891@PubMed]
	Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450-2C19 (CYP2C19) Genotype and Clopidogrel Therapy. Clinical pharmacology and therapeutics. 2011. Scott S A, et al. [Article:21716271@PubMed]
	Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. [Article:21412232@PubMed]
	The missing association: sequencing-based discovery of NOVEL SNPs in VKORC1 and CYP2C9 that affect warfarin dose in African Americans. Clinical pharmacology and therapeutics. 2011. Perera M A, et al. [Article:21270790@PubMed]
	Complex Drug Interactions of HIV Protease Inhibitors 2: In Vivo Induction and In Vitro to In Vivo Correlation of Induction of Cytochrome P450 1A2, 2B6 and 2C9 by Ritonavir or Nelfinavir. Drug metabolism and disposition: the biological fate of chemicals. 2011. Kirby Brian J, et al. [Article:21930825@PubMed]
	A candidate gene study of antiepileptic drug tolerability and efficacy identifies an association of CYP2C9 variants with phenytoin toxicity. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2011. Depondt C, et al. [Article:21338443@PubMed]
	Pharmacogenetics of Coumarin Dosing: Prevalence of CYP2C9 and VKORC1 Polymorphisms in the Lebanese Population. Genetic testing and molecular biomarkers. 2011. Djaffar-Jureidini Isabelle, et al. [Article:21651319@PubMed]
VA	Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people. Journal of clinical pharmacology. 2011. Esmerian Maria O, et al. [Article:21148049@PubMed]
	Genetic warfarin dosing tables versus algorithms. Journal of the American College of Cardiology. 2011. Finkelman Brian S, et al. [Article:21272753@PubMed]
	Facilitating pharmacogenetic studies using electronic health records and natural-language processing: a case study of warfarin. Journal of the American Medical Informatics Association : JAMIA. 2011. Xu Hua, et al. [Article:21672908@PubMed]
	Genetic and nongenetic factors associated with warfarin doserequirements in Egyptian patients. Pharmacogenetics and genomics. 2011. Shahin Mohamed Hossam A, et al. [Article:21228733@PubMed]
	Comparison of warfarin pharmacogenetic dosing algorithms in a racially diverse large cohort. Pharmacogenomics. 2011. Shin Jaekyu, et al. [Article:21174627@PubMed]
	Copy number variation and warfarin dosing: evaluation of CYP2C9, VKORC1, CYP4F2, GGCX and CALU. Pharmacogenomics. 2011. Scott Stuart A, et al. [Article:22188360@PubMed]
	Genetic variants in CYP (-1A2, -2C9, -2C19, -3A4 and -3A5), VKORC1 and ABCB1 genes in a black South African population: a window into diversity. Pharmacogenomics. 2011. Dandara Collet, et al. [Article:22118051@PubMed]
VA	Novel CYP2C9 and VKORC1 gene variants associated with warfarin dosage variability in the South African black population. Pharmacogenomics. 2011. Mitchell Cathrine, et al. [Article:21635147@PubMed]
	Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. [Article:21174626@PubMed]
	Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group. Pharmacogenomics. 2011. Patterson Scott D, et al. [Article:21787188@PubMed]
	Clinical and Genetic Determinants of Warfarin Pharmacokinetics and Pharmacodynamics during Treatment Initiation. PloS one. 2011. Gong Inna Y, et al. [Article:22114699@PubMed]
VA	Possible role of CYP2C9 & CYP2C19 single nucleotide polymorphisms in drug refractory epilepsy. The Indian journal of medical research. 2011. Lakhan Ram, et al. [Article:21985811@PubMed]
	Genomics and drug response. The New England journal of medicine. 2011. Wang Liewei, et al. [Article:21428770@PubMed]
	Cytochrome P450 Polymorphisms and their Relationship with Premature Ovarian Failure in Premenopausal Women with Breast Cancer Receiving Doxorubicin and Cyclophosphamide. The breast journal. 2011. Wessels Alette M, et al. [Article:21827565@PubMed]
	Genetics informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT): rationale and study design. The pharmacogenomics journal. 2011. Do E J, et al. [Article:21606949@PubMed]
	Optimization of warfarin dose by population-specific pharmacogenomic algorithm. The pharmacogenomics journal. 2011. Pavani A, et al. [Article:21358752@PubMed]
	Translational aspects of genetic factors in the prediction of drug response variability: a case study of warfarin pharmacogenomics in a multi-ethnic cohort from Asia. The pharmacogenomics journal. 2011. Chan S L, et al. [Article:21383771@PubMed]
	Contributions of human cytochrome P450 enzymes to glyburide metabolism. Biopharmaceutics & drug disposition. 2010. Zhou Lin, et al. [Article:20437462@PubMed]
	In pediatric patients, age has more impact on dosing of vitamin K antagonists than VKORC1 or CYP2C9 genotypes. Blood. 2010. Nowak-Göttl Ulrike, et al. [Article:20833980@PubMed]
	Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood. 2010. Limdi Nita A, et al. [Article:20203262@PubMed]
	Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study. Breast cancer research : BCR. 2010. Gor Priya P, et al. [Article:20459744@PubMed]
VA	The influence of cytochrome oxidase CYP2A6, CYP2B6, and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients. Clinical neurology and neurosurgery. 2010. Tan Lan, et al. [Article:20089352@PubMed]
	A Phenotype-Genotype Approach to Predicting CYP450 and P-Glycoprotein Drug Interactions With the Mixed Inhibitor/Inducer Tipranavir/Ritonavir. Clinical pharmacology and therapeutics. 2010. Dumond J B, et al. [Article:20147896@PubMed]
	A pharmacometric model describing the relationship between warfarin dose and INR response with respect to variations in CYP2C9, VKORC1, and age. Clinical pharmacology and therapeutics. 2010. Hamberg A-K, et al. [Article:20410877@PubMed]
	A polymorphism in the VKORC1 regulator calumenin predicts higher warfarin dose requirements in African Americans. Clinical pharmacology and therapeutics. 2010. Voora D, et al. [Article:20200517@PubMed]
	CYP2C93 Loss-of-Function Allele Is Associated With Acute Upper Gastrointestinal Bleeding Related to the Use of NSAIDs Other Than Aspirin. Clinical pharmacology and therapeutics.* 2010. Carbonell N, et al. [Article:20445534@PubMed]
	Clinically significant CYP2C inhibition by noscapine but not by glucosamine. Clinical pharmacology and therapeutics. 2010. Rosenborg S, et al. [Article:20668444@PubMed]
	Gemfibrozil markedly increases the plasma concentrations of montelukast: a previously unrecognized role for CYP2C8 in the metabolism of montelukast. Clinical pharmacology and therapeutics. 2010. Karonen T, et al. [Article:20592724@PubMed]
CA	Genetic and clinical predictors of warfarin dose requirements in African Americans. Clinical pharmacology and therapeutics. 2010. Cavallari L H, et al. [Article:20072124@PubMed]
	Genetic and clinical predictors of warfarin dose requirements in African Americans. Clinical pharmacology and therapeutics. 2010. Cavallari L H, et al. [Article::20072124@PubMed]
CA	Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clinical pharmacology and therapeutics. 2010. Pautas E, et al. [Article:19794411@PubMed]
	Integration of genetic, clinical, and INR data to refine warfarin dosing. Clinical pharmacology and therapeutics. 2010. Lenzini P, et al. [Article:20375999@PubMed]
CA	Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study. Clinical pharmacology and therapeutics. 2010. Zhou K, et al. [Article:19794412@PubMed]
	Transporter pharmacogenetics and statin toxicity. Clinical pharmacology and therapeutics. 2010. Niemi M. [Article:19890253@PubMed]
	Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug metabolism and disposition: the biological fate of chemicals. 2010. Kazui Miho, et al. [Article:19812348@PubMed]
	New insights into the regulation of CYP2C9 gene expression: the role of the transcription factor GATA-4. Drug metabolism and disposition: the biological fate of chemicals. 2010. Mwinyi Jessica, et al. [Article:19995889@PubMed]
	Linkage disequilibrium between the CYP2C1917 allele and wildtype CYP2C8 and CYP2C9 alleles: identification of CYP2C haplotypes in healthy Nordic populations. European journal of clinical pharmacology.* 2010. Pedersen Rasmus S, et al. [Article:20665013@PubMed]
	Expectations, validity, and reality in pharmacogenetics. Journal of clinical epidemiology. 2010. Limdi Nita A, et al. [Article:19995676@PubMed]
	Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. Journal of clinical pharmacology. 2010. Farid Nagy A, et al. [Article:19948947@PubMed]
	Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. Journal of human genetics. 2010. Ross Kendra A, et al. [Article:20555338@PubMed]
	Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study). Journal of the American College of Cardiology. 2010. Epstein Robert S, et al. [Article:20381283@PubMed]
	Ability of VKORC1 and CYP2C9 to predict therapeutic warfarin dose during the initial weeks of therapy. Journal of thrombosis and haemostasis : JTH. 2010. Ferder N S, et al. [Article:19874474@PubMed]
	Besides CYP2C192, the variant allele CYP2C93 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation. Pharmacogenetics and genomics. 2010. Harmsze Ankie, et al. [Article:19934793@PubMed]
PW	Clopidogrel pathway. Pharmacogenetics and genomics. 2010. Sangkuhl Katrin, et al. [Article:20440227@PubMed]
VIP	Cytochrome P450 2C9-CYP2C9. Pharmacogenetics and genomics. 2010. Van Booven Derek, et al. [Article:20150829@PubMed]
	Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9. Pharmacogenetics and genomics. 2010. Sagreiya Hersh, et al. [Article:20442691@PubMed]
	Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups. Pharmacogenomics. 2010. Scott Stuart A, et al. [Article:20504253@PubMed]
VA	Effect of CYP2C9 polymorphisms on prescribed dose and time-to-stable dose of sulfonylureas in primary care patients with Type 2 diabetes mellitus. Pharmacogenomics. 2010. Swen Jesse J, et al. [Article:21121772@PubMed]
	Genetic profile of patients with epilepsy on first-line antiepileptic drugs and potential directions for personalized treatment. Pharmacogenomics. 2010. Grover Sandeep, et al. [Article:20602612@PubMed]
VA	Impact of CYP2C8 and 2C9 polymorphisms on coronary artery disease and myocardial infarction in the LURIC cohort. Pharmacogenomics. 2010. Haschke-Becher Elisabeth, et al. [Article:21047199@PubMed]
	Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. [Article:21121811@PubMed]
	VKORC1, CYP2C9 and CYP4F2 genetic-based algorithm for warfarin dosing: an Italian retrospective study. Pharmacogenomics. 2010. Zambon Carlo-Federico, et al. [Article:21174619@PubMed]
	Pharmacogenomics: role in medicines approval and clinical use. Public health genomics. 2010. Novelli G, et al. [Article:19815999@PubMed]
VA	CYP2C91B promoter polymorphisms, in linkage with CYP2C192, affect phenytoin autoinduction of clearance and maintenance dose. The Journal of pharmacology and experimental therapeutics. 2010. Chaudhry Amarjit S, et al. [Article:19855097@PubMed]
	Changes in the gene expression profile of gastric cancer cells in response to ibuprofen: a gene pathway analysis. The pharmacogenomics journal. 2010. Bonelli P, et al. [Article:20548326@PubMed]
	Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians. The pharmacogenomics journal. 2010. Suarez-Kurtz G, et al. [Article:21173785@PubMed]
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	Effect of genetic polymorphisms in cytochrome p450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs: clinical relevance. Clinical pharmacokinetics. 2005. Kirchheiner Julia, et al. [Article:16372821@PubMed]
	Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clinical pharmacokinetics. 2005. Kosoglou Teddy, et al. [Article:15871634@PubMed]
	CYP2C9, but not CYP2C19, polymorphisms affect the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects. Clinical pharmacology and therapeutics. 2005. Yin Ophelia Q P, et al. [Article:16198656@PubMed]
VIP	Clinical consequences of cytochrome P450 2C9 polymorphisms. Clinical pharmacology and therapeutics. 2005. Kirchheiner Julia, et al. [Article:15637526@PubMed]
	Common genetic variants of microsomal epoxide hydrolase affect warfarin dose requirements beyond the effect of cytochrome P450 2C9. Clinical pharmacology and therapeutics. 2005. Loebstein Ronen, et al. [Article:15900282@PubMed]
VA	Cytochrome P450 2C9 genotype: impact on celecoxib safety and pharmacokinetics in a pediatric patient. Clinical pharmacology and therapeutics. 2005. Stempak Diana, et al. [Article:16153401@PubMed]
	Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam. Clinical pharmacology and therapeutics. 2005. Perini Jamila A, et al. [Article:16198655@PubMed]
	Pharmacokinetics of glimepiride and cytochrome P450 2C9 genetic polymorphisms. Clinical pharmacology and therapeutics. 2005. Wang Rui, et al. [Article:16003298@PubMed]
VIP	Impact of CYP2C9 genotype on pharmacokinetics: are all cyclooxygenase inhibitors the same?. Drug metabolism and disposition: the biological fate of chemicals. 2005. Rodrigues A David. [Article:16118328@PubMed]
	CYP2C9, CYP2C19, ABCB1 (MDR1) genetic polymorphisms and phenytoin metabolism in a Black Beninese population. Pharmacogenetics and genomics. 2005. Allabi Aurel C, et al. [Article:16220110@PubMed]
	In-vitro and in-vivo effects of the CYP2C911 polymorphism on warfarin metabolism and dose. Pharmacogenetics and genomics.* 2005. Tai Guoying, et al. [Article:15970795@PubMed]
VA	Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proceedings of the National Academy of Sciences of the United States of America. 2005. Tate Sarah K, et al. [Article:15805193@PubMed]
	Differential activation of CYP2C9 variants by dapsone. Biochemical pharmacology. 2004. Hummel Matthew A, et al. [Article:15130760@PubMed]
VA	Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. British journal of pharmacology. 2004. Martínez Carmen, et al. [Article:14707031@PubMed]
	United States Food and Drug Administration Drug Approval summary: Gefitinib (ZD1839; Iressa) tablets. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004. Cohen Martin H, et al. [Article:14977817@PubMed]
	CYP2C9 genotypes and the pharmacokinetics of tenoxicam in Brazilians. Clinical pharmacology and therapeutics. 2004. Vianna-Jorge Rosane, et al. [Article:15229460@PubMed]
	Functional impact of CYP2C95, CYP2C96, CYP2C98, and CYP2C911 in vivo among black Africans. Clinical pharmacology and therapeutics. 2004. Allabi Aurel C, et al. [Article:15289788@PubMed]
CA	Pharmacogenetics of acenocoumarol pharmacodynamics. Clinical pharmacology and therapeutics. 2004. Morin Sandrine, et al. [Article:15116053@PubMed]
	CYP2C9 genetic variants and losartan oxidation in a Turkish population. European journal of clinical pharmacology. 2004. Babaoglu Melih O, et al. [Article:15197523@PubMed]
	A novel CYP2C9 variant that caused erroneous genotyping in a patient on warfarin therapy. Pharmacogenetics. 2004. Okuda Rika, et al. [Article:15454736@PubMed]
VA	Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics. 2004. Blaisdell Joyce, et al. [Article:15284535@PubMed]
	Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype. Pharmacogenetics. 2004. Hillman Michael A, et al. [Article:15284536@PubMed]
	Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism. Pharmacogenetics. 2004. King Barry P, et al. [Article:15608560@PubMed]
	Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. The pharmacogenomics journal. 2004. Wadelius M, et al. [Article:14676821@PubMed]
	Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annual review of pharmacology and toxicology. 2003. Ding Xinxin, et al. [Article:12171978@PubMed]
	Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (-)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers. Clinical pharmacology and therapeutics. 2003. Kirchheiner Julia, et al. [Article:12891229@PubMed]
	Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients. Clinical pharmacology and therapeutics. 2003. Takahashi Harumi, et al. [Article:12621390@PubMed]
	A new class of CYP2C9 inhibitors: probing 2C9 specificity with high-affinity benzbromarone derivatives. Drug metabolism and disposition: the biological fate of chemicals. 2003. Locuson Charles W, et al. [Article:12814975@PubMed]
	Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug metabolism and disposition: the biological fate of chemicals. 2003. Madan Ajay, et al. [Article:12642468@PubMed]
	Clinical relevance of genetic polymorphisms in the human CYP2C9 gene. European journal of clinical investigation. 2003. Schwarz U I. [Article:14641553@PubMed]
VIP	Bioactivation of cyclophosphamide: the role of polymorphic CYP2C enzymes. European journal of clinical pharmacology. 2003. Griskevicius Laimonas, et al. [Article:12684728@PubMed]
	Effect of the single CYP2C93 allele on pharmacokinetics and pharmacodynamics of losartan in healthy Japanese subjects. European journal of clinical pharmacology.* 2003. Sekino Kazuishi, et al. [Article:14504849@PubMed]
	Genetic and environmental risk factors for oral anticoagulant overdose. European journal of clinical pharmacology. 2003. Verstuyft C, et al. [Article:12634980@PubMed]
	No major difference in inhibitory susceptibility between CYP2C9.1 and CYP2C9.3. European journal of clinical pharmacology. 2003. Hanatani Tadaaki, et al. [Article:12756514@PubMed]
	Allelic variants of cytochromes P450 2C modify the risk for acute myocardial infarction. Pharmacogenetics. 2003. Yasar Umit, et al. [Article:14646690@PubMed]
VA VIP	Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites. Pharmacogenetics. 2003. Kirchheiner Julia, et al. [Article:12893985@PubMed]
	Losartan and E3174 pharmacokinetics in cytochrome P450 2C91/1, 1/2, and 1/3 individuals. Pharmacotherapy. 2003. Lee Craig R, et al. [Article:12820813@PubMed]
VA	Influence of CYP2C9 genotypes on the formation of a hepatotoxic metabolite of valproic acid in human liver microsomes. The pharmacogenomics journal. 2003. Ho P C, et al. [Article:14597963@PubMed]
	Differential effects of 2C93 and 2C92 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol. Blood. 2002. Hermida José, et al. [Article:12010835@PubMed]
	CYP2C9 polymorphism and warfarin dose requirements. British journal of clinical pharmacology. 2002. Daly Ann K, et al. [Article:11966680@PubMed]
	Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clinical pharmacology and therapeutics. 2002. Kirchheiner Julia, et al. [Article:12152005@PubMed]
	Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clinical pharmacology and therapeutics. 2002. Niemi Mikko, et al. [Article:12235454@PubMed]
	Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clinical pharmacology and therapeutics. 2002. Kirchheiner Julia, et al. [Article:11956512@PubMed]
	Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clinical pharmacology and therapeutics. 2002. Scordo Maria Gabriella, et al. [Article:12496751@PubMed]
	Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clinical pharmacology and therapeutics. 2002. Yasar Umit, et al. [Article:11823761@PubMed]
	Involvement of multiple UDP-glucuronosyltransferase 1A isoforms in glucuronidation of 5-(4'-hydroxyphenyl)-5-phenylhydantoin in human liver microsomes. Drug metabolism and disposition: the biological fate of chemicals. 2002. Nakajima Miki, et al. [Article:12386132@PubMed]
	Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolism. Drug metabolism and disposition: the biological fate of chemicals. 2002. Rae James M, et al. [Article:11950782@PubMed]
	Analysis of CYP2C95 in Caucasian, Oriental and black-African populations. European journal of clinical pharmacology.* 2002. Yasar Umit, et al. [Article:12451434@PubMed]
VIP	Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA : the journal of the American Medical Association. 2002. Higashi Mitchell K, et al. [Article:11926893@PubMed]
	The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. Journal of hypertension. 2002. Hallberg Pär, et al. [Article:12359989@PubMed]
	Warfarin dose adjustments based on CYP2C9 genetic polymorphisms. Journal of thrombosis and thrombolysis. 2002. Linder Mark W, et al. [Article:12913403@PubMed]
	Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics. 2002. Lee Craig R, et al. [Article:11927841@PubMed]
	Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans. Pharmacogenetics. 2002. Shon Ji-Hong, et al. [Article:11875365@PubMed]
	Med-psych drug-drug interactions update. Psychosomatics. 2002. Armstrong Scott C, et al. [Article:11927765@PubMed]
	Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes. The Journal of biological chemistry. 2002. Drocourt Lionel, et al. [Article:11991950@PubMed]
	Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes. Acta pharmacologica Sinica. 2001. Liu Z Q, et al. [Article:11730569@PubMed]
	In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). British journal of clinical pharmacology. 2001. Wen X, et al. [Article:11736863@PubMed]
	Clinical pharmacokinetics of fluvastatin. Clinical pharmacokinetics. 2001. Scripture C D, et al. [Article:11368292@PubMed]
	Pharmacogenetics of warfarin elimination and its clinical implications. Clinical pharmacokinetics. 2001. Takahashi H, et al. [Article:11523725@PubMed]
	Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug metabolism and disposition: the biological fate of chemicals. 2001. Drocourt L, et al. [Article:11560876@PubMed]
VA	Role of CYP2C9 polymorphism in losartan oxidation. Drug metabolism and disposition: the biological fate of chemicals. 2001. Yasar U, et al. [Article:11408373@PubMed]
	Identification and functional characterization of a new CYP2C9 variant (CYP2C95) expressed among African Americans. Molecular pharmacology.* 2001. Dickmann L J, et al. [Article:11455026@PubMed]
CA VA	Early acenocoumarol overanticoagulation among cytochrome P450 2C9 poor metabolizers. Pharmacogenetics. 2001. Verstuyft C, et al. [Article:11692083@PubMed]
	Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics. 2001. Kidd R S, et al. [Article:11740344@PubMed]
VA	In-vitro metabolism of celecoxib, a cyclooxygenase-2 inhibitor, by allelic variant forms of human liver microsomal cytochrome P450 2C9: correlation with CYP2C9 genotype and in-vivo pharmacokinetics. Pharmacogenetics. 2001. Tang C, et al. [Article:11337938@PubMed]
	The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics. 2001. van der Weide J, et al. [Article:11434505@PubMed]
	Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. The Journal of biological chemistry. 2001. Dussault I, et al. [Article:11466304@PubMed]
	Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays. The Journal of pharmacology and experimental therapeutics. 2001. Rae J M, et al. [Article:11714868@PubMed]
	Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharmaceutics & drug disposition. 2000. Cohen L H, et al. [Article:11523064@PubMed]
	Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood. 2000. Taube J, et al. [Article:10961881@PubMed]
	Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4. Drug metabolism and disposition: the biological fate of chemicals. 2000. Komatsu T, et al. [Article:11038165@PubMed]
	Phenytoin metabolism by human cytochrome P450: involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation. Drug metabolism and disposition: the biological fate of chemicals. 2000. Cuttle L, et al. [Article:10901705@PubMed]
	Major role of human liver microsomal cytochrome P450 2C9 (CYP2C9) in the oxidative metabolism of celecoxib, a novel cyclooxygenase-II inhibitor. The Journal of pharmacology and experimental therapeutics. 2000. Tang C, et al. [Article:10773015@PubMed]
CA VA	Genetic modulation of oral anticoagulation with warfarin. Thrombosis and haemostasis. 2000. Margaglione M, et al. [Article:11127854@PubMed]
	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Archives of toxicology. 1999. Yamazaki H, et al. [Article:10350185@PubMed]
	Phenotypic and genotypic investigations of a healthy volunteer deficient in the conversion of losartan to its active metabolite E-3174. Clinical pharmacology and therapeutics. 1999. McCrea J B, et al. [Article:10096267@PubMed]
	Role of cytochrome P-4502C9 in irbesartan oxidation by human liver microsomes. Drug metabolism and disposition: the biological fate of chemicals. 1999. Bourrié M, et al. [Article:9929518@PubMed]
	The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug metabolism and disposition: the biological fate of chemicals. 1999. Fischer V, et al. [Article:10064574@PubMed]
	Inhibition of CYP2C9 by selective serotonin reuptake inhibitors: in vitro studies with tolbutamide and (S)-warfarin using human liver microsomes. European journal of clinical pharmacology. 1999. Hemeryck A, et al. [Article:10192756@PubMed]
	The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers. Journal of clinical pharmacology. 1999. Meadowcroft A M, et al. [Article:10197301@PubMed]
VIP	Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet. 1999. Aithal G P, et al. [Article:10073515@PubMed]
	Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C93 allele. Pharmacogenetics.* 1999. Kidd R S, et al. [Article:10208645@PubMed]
	Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys- and Leu-variants in the oxidation of warfarin, flurbiprofen, and diclofenac by human liver microsomes. Biochemical pharmacology. 1998. Yamazaki H, et al. [Article:9698079@PubMed]
VIP	Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. British journal of clinical pharmacology. 1998. Miners J O, et al. [Article:9663807@PubMed]
	Comparisons between in-vitro and in-vivo metabolism of (S)-warfarin: catalytic activities of cDNA-expressed CYP2C9, its Leu359 variant and their mixture versus unbound clearance in patients with the corresponding CYP2C9 genotypes. Pharmacogenetics. 1998. Takahashi H, et al. [Article:9825828@PubMed]
	Genetic association between sensitivity to warfarin and expression of CYP2C93. Pharmacogenetics.* 1997. Steward D J, et al. [Article:9352571@PubMed]
	The R144C change in the CYP2C92 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. Pharmacogenetics.* 1997. Crespi C L, et al. [Article:9241660@PubMed]
	Human CYP2C9 and CYP2A6 mediate formation of the hepatotoxin 4-ene-valproic acid. The Journal of pharmacology and experimental therapeutics. 1997. Sadeque A J, et al. [Article:9353388@PubMed]
	Allelic variants of human cytochrome P450 2C9: baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms. Archives of biochemistry and biophysics. 1996. Haining R L, et al. [Article:8809086@PubMed]
	Putative active site template model for cytochrome P4502C9 (tolbutamide hydroxylase). Drug metabolism and disposition: the biological fate of chemicals. 1996. Jones B C, et al. [Article:8742240@PubMed]
	Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereoselective metabolism of phenytoin to its major metabolite. Drug metabolism and disposition: the biological fate of chemicals. 1996. Bajpai M, et al. [Article:8971149@PubMed]
	The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics. 1996. Sullivan-Klose T H, et al. [Article:8873220@PubMed]
	In vivo inhibition profile of cytochrome P450TB (CYP2C9) by (+/-)-fluvastatin. Clinical pharmacology and therapeutics. 1995. Transon C, et al. [Article:7586933@PubMed]
	Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans. Clinical pharmacology and therapeutics. 1995. Lo M W, et al. [Article:8529329@PubMed]
VIP	A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24. Genomics. 1995. Gray I C, et al. [Article:8530044@PubMed]
	Human hepatic cytochrome P450 2C9 catalyzes the rate-limiting pathway of torsemide metabolism. The Journal of pharmacology and experimental therapeutics. 1995. Miners J O, et al. [Article:7891318@PubMed]
	Stereochemical aspects of warfarin drug interactions: use of a combined pharmacokinetic-pharmacodynamic model. Clinical pharmacology and therapeutics. 1994. Chan E, et al. [Article:7924124@PubMed]
	O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4. Molecular pharmacology. 1994. Relling M V, et al. [Article:8114683@PubMed]
	Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chemical research in toxicology. 1992. Rettie A E, et al. [Article:1581537@PubMed]
	Effect of fluconazole on the disposition of phenytoin. Clinical pharmacology and therapeutics. 1991. Blum R A, et al. [Article:2015731@PubMed]
	Mechanism of warfarin potentiation by amiodarone: dose--and concentration--dependent inhibition of warfarin elimination. European journal of clinical pharmacology. 1985. Almog S, et al. [Article:4007030@PubMed]
	Clinical importance of the interaction of phenytoin and isoniazid: a report from the Boston Collaborative Drug Surveillance Program. Chest. 1979. Miller R R, et al. [Article:421578@PubMed]

Datasets

LinkOuts

Entrez Gene:: 1559
OMIM:: 122700; 601130
UCSC Genome Browser:: NM_000771
RefSeq RNA:: NM_000771
RefSeq Protein:: NP_000762
RefSeq DNA:: AC_000053; AC_000142; NC_000010; NG_008385; NT_030059; NW_001838005; NW_924884

Web Resource:: http://www.imm.ki.se/CYPalleles/cyp2c9.htm
UniProtKB:: CP2C9_HUMAN (P11712); Q5VX92_HUMAN (Q5VX92)
Ensembl:: ENSG00000138109
GenAtlas:: CYP2C9
GeneCard:: GC10P096688 (1559)
MutDB:: CYP2C9

ALFRED:: LO000304H
HuGE:: CYP2C9
Comparative Toxicogenomics Database:: 1559
ModBase:: P11712
HumanCyc Gene:: HS06458
HGNC:: 2623

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©2001-2012 PharmGKB.

Gene: CYP2C9 cytochrome P450, family 2, subfamily C, polypeptide 9

Excerpt from the warfarin dosing guidelines:

Excerpt from the warfarin dosing guidelines:

Table 1: Recommended daily warfarin doses (mg/day) to achieve a therapeutic INR based on CYP2C9 and VKORC1 genotype using the warfarin product insert approved by the United States Food and Drug Administration:

Supplemental Table S1. Genotypes that constitute the * alleles for CYP2C9

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Curated Information ?

Publications related to CYP2C9: 329

Datasets

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Gene:
CYP2C9
cytochrome P450, family 2, subfamily C, polypeptide 9