Drug/Small Molecule:
valproic acid

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for valproic acid and OTC, POLG

This label is on the FDA Biomarker List
Genetic testing required

Summary

Valproic acid is used to treat patients with various types of seizures. This drug has a black box warning for several adverse events including pancreatitis, liver failure and death, and major congenital malformations such as neural tube defects from exposure in utero.

Annotation

Treatment with valproic acid is contraindicated in patients with known urea cycle disorders (UCD), a group of uncommon genetic abnormalities, since these patients can experience sometimes fatal hyperammonemic encephalopathy following initiation of valproate therapy. UCD results from mutations in one of several genes, including ornithine transcarbamylase (OTC) deficiency and carbamoyl-phosphate synthetase 1 (CPS1) deficiency.

Excerpt from the valproic acid (Depakene) drug label:

Valproic acid is contraindicated in patients with known urea cycle disorders.

Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders, a group of uncommon genetic abnormalities, particularly ornithine transcarbamylase deficiency. Prior to the initiation of valproate therapy, evaluation for UCD should be considered in the following patients: 1) those with a history of unexplained encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine; 2) those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low blood urea nitrogen (BUN), or protein avoidance; 3) those with a family history of UCD or a family history of unexplained infant deaths (particularly males); 4) those with other signs or symptoms of UCD.

Valproic acid is also contraindicated in patients with POLG mutations. POLG is a mitochondrial DNA polymerase and mutations in this gene are associated with hereditary neurometabolic syndromes such as Alpers Huttenlocher Syndrome. These patients are at an increased risk of liver failure and death.

POLG mutation testing should be performed in accordance with current clinical practice for the diagnostic evaluation of such disorders. The A467T and W748S mutations are present in approximately 2/3 of patients with autosomal recessive POLG-related disorders.

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

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

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Bipolar Disorder
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Congenital Abnormalities
    • Warnings section
    • source: PHONT
  • Epilepsy
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Headache
    • Indications & usage section, Adverse reactions section
    • source: PHONT
  • Leukemia, Myeloid, Acute
    • Warnings section, Precautions section
    • source: PHONT
  • Migraine without Aura
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Neoplasms
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Pancreatitis
    • Boxed warning section, Adverse reactions section, Warnings and precautions section
    • source: FDA Label
  • Seizures
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Spinal Dysraphism
    • Warnings section
    • source: PHONT
  • Toxic liver disease
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • OTC
    • Contraindications section, Warnings and precautions section, toxicity
    • source: FDA Label
  • POLG
    • Boxed warning section, Contraindications section, Warnings and precautions section, toxicity
    • source: FDA Label

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

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

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

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and 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.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

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 "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA CYP2A6 *1A N/A N/A N/A
No VIP available No VIP available VA CYP2A6 *4A N/A N/A N/A
No VIP available No VIP available VA HLA-B *15:02:01 N/A N/A N/A
No VIP available CA VA UGT1A6 *1a N/A N/A N/A
No VIP available CA VA UGT1A6 *2a N/A N/A N/A
No VIP available CA VA UGT1A6 *3a N/A N/A N/A
No VIP available CA VA UGT1A6 *4a N/A N/A N/A
No VIP available CA VA UGT1A6 *8 N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs10068980 161287847G>A, 18651G>A, 188-4880G>A, 6099120G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs1019385 -2000G>T, 14134843C>A, 3180G>T, 6894967C>A
C > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
No VIP available No Clinical Annotations available VA
rs1047891 203099C>A, 211540507C>A, 2864C>A, 4217C>A, 4235C>A, 61749925C>A, Thr1406Asn, Thr1412Asn, Thr955Asn
C > A
Missense
Thr955Asn
No VIP available No Clinical Annotations available VA
rs1057910 1075A>C, 47545517A>C, 47639A>C, 96741053A>C, CYP2C9*3, CYP2C9*3:Ile359Leu, CYP2C9: I359L, CYP2C9:359Ile>Leu, CYP2C9:Ile359Leu, Ile359Leu, mRNA 11A>C
A > C
Missense
Ile359Leu
No VIP available CA VA
rs1105879 -7-243A>C, 108813A>C, 234602202A>C, 548461A>C, 552A>C, 855+10764A>C, 855+20767A>C, 855+56179A>C, 856-73478A>C, Arg184Ser
A > C
Intronic
Arg184Ser
No VIP available No Clinical Annotations available VA
rs1112122 -27+13614C>A, 151606004G>T, 18827C>A, 2523942G>T
G > T
Intronic
No VIP available No Clinical Annotations available VA
rs1128503 1236T>C, 167964T>C, 25043506A>G, 87550285A>G, ABCB1 1236C>T, ABCB1*8, ABCB1: c.1236T>C, ABCB1:1236C>T, ABCB1:1236T>C, Gly412=, Gly412Gly, mRNA 1654T>C, p.Gly412Gly
A > G
Not Available
Gly412Gly
No VIP available No Clinical Annotations available VA
rs1157122 161319314T>C, 50118T>C, 6130587T>C, 856+1258T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs1565445 16781603G>A, 2125-18050G>A, 2173-18050G>A, 338606G>A, 87617071G>A
G > A
Intronic
No VIP available CA VA
rs17183814 16361807G>A, 166152389G>A, 56G>A, 61478G>A, Arg19Lys
G > A
Missense
Arg19Lys
No VIP available No Clinical Annotations available VA
rs1799853 430C>T, 47506511C>T, 8633C>T, 96702047C>T, Arg144Cys, CYP2C9*2, CYP2C9:144Arg>Cys, CYP2C9:Arg144Cys, mRNA 455C>T
C > T
Missense
Arg144Cys
No VIP available No Clinical Annotations available VA
rs1799883 120241902T>A, 120241902T>C, 120241902T>G, 163A>C, 163A>G, 163A>T, 44789623T>A, 44789623T>C, 44789623T>G, 6415A>C, 6415A>G, 6415A>T, Thr55Ala, Thr55Pro, Thr55Ser
T > G
T > A
T > C
Missense
Thr55Ala
No VIP available No Clinical Annotations available VA
rs2032582 186947T>A, 186947T>G, 25193461A>C, 25193461A>T, 2677A, 2677G, 2677T, 2677T>A, 2677T>G, 3095G>T/A, 87160618A>C, 87160618A>T, 893 Ala, 893 Ser, 893 Thr, ABCB1*7, ABCB1: 2677G>T/A, ABCB1: 2677T/A>G, ABCB1: A893S, ABCB1: G2677T/A, ABCB1: c.2677G>T/A, ABCB1:2677G>A/T, ABCB1:2677G>T/A, ABCB1:A893T, Ala893Ser/Thr, MDR1, MDR1 G2677T/A, Ser893Ala, Ser893Thr, mRNA 3095G>T/A, p.Ala893Ser/Thr
A > C
A > T
Missense
Ser893Ala
Ser893Thr
No VIP available CA VA
rs2070959 -7-254A>G, 108802A>G, 234602191A>G, 541A>G, 548450A>G, 855+10753A>G, 855+20756A>G, 855+56168A>G, 856-73489A>G, Thr181Ala
A > G
Intronic
Thr181Ala
No VIP available No Clinical Annotations available VA
rs211037 161528280C>T, 38633C>T, 588C>T, 6339553C>T, Asn196=
C > T
Synonymous
Asn196Asn
No VIP available No Clinical Annotations available VA
rs2229944 1194C>T, 1308C>T, 160721319G>A, 5532592G>A, Ala398=, Ala436=
G > A
Synonymous
Ala436Ala
No VIP available No Clinical Annotations available VA
rs2269577 -245C>G, 29196757G>C, 4804C>G, 8587326G>C
G > C
5' Flanking
No VIP available CA VA
rs2279020 1059+15G>A, 161322889G>A, 53693G>A, 6134162G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs2298771
C > T
Not Available
Ala1056Thr
No VIP available No Clinical Annotations available VA
rs2606345 -27+606G>T, 45807733C>A, 7294C>A, 75017176C>A
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs2741049 234581834T>C, 528093T>C, 855+35811T>C, 855+399T>C, 855+54626T>C, 88445T>C
T > C
Intronic
No VIP available CA VA
rs2769605 17077203C>T, 87912671C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs28365062 10174938A>G, 69964271A>G, 735A>G, Thr245=
A > G
Synonymous
Thr245Thr
No VIP available No Clinical Annotations available VA
rs3219151 *135C>T, 161128914C>T, 5940187C>T
C > T
3' UTR
No VIP available No Clinical Annotations available VA
rs3812718 166909544C>T, 17118962C>T, 25606G>A, 603-91G>A
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs4244285 24154G>A, 24154G>C, 47346080G>A, 47346080G>C, 681G>A, 681G>C, 96541616G>A, 96541616G>C, CYP2C19*2, CYP2C19:681G>A, CYP2C19:G681A, Pro227=
G > C
G > A
Synonymous
Pro227Pro
VIP No Clinical Annotations available No Variant Annotations available
rs4680 1-5G>A, 19951271G>A, 27009G>A, 3103421G>A, 322G>A, 472G>A, COMP: Val158Met, COMT:Val108Met, Val108Met, Val158Met
G > A
5' Flanking
Val158Met
No VIP available No Clinical Annotations available VA
rs4828696 -27+37622A>G, 151581996T>C, 2499934T>C, 42835A>G
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs511310 46240004A>G, 5942908A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs6731242 -1888T>G, 234578693T>G, 524952T>G, 85304T>G, 855+32670T>G, 855+51485T>G
T > G
5' Flanking
No VIP available CA VA
rs6759892 -7-776T>G, 108280T>G, 19T>G, 234601669T>G, 547928T>G, 855+10231T>G, 855+20234T>G, 855+55646T>G, 856-74011T>G, Ser7Ala
T > G
Intronic
Ser7Ala
No VIP available No Clinical Annotations available VA
rs6883877 161278338C>T, 6089611C>T, 74+448C>T, 9142C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs6892782 161269783T>C, 587T>C, 6081056T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs7438284 10175004A>T, 69964337A>T, 801A>T, Pro267=
A > T
Synonymous
Pro267Pro
No VIP available CA VA
rs7439366 10175005T>C, 69964338T>C, 802T>C, Tyr268His, UGT2B7*2, UGT2B7:802C>T, UGT2B7:H268Y, UGT2B7Y
T > C
Missense
Tyr268His
No VIP available No Clinical Annotations available VA
rs7668258 -161T>C, 10172745T>C, 69962078T>C
T > C
5' Flanking
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • 2-propylvaleric acid
  • DPA
  • Di-n-propylacetic acid
  • Di-n-propylessigsaure
  • Dipropylacetic acid
  • Kyselina 2-propylvalerova
  • Myproic Acid
  • Propylvaleric acid
  • Sodium hydrogen divalproate
  • VPA
  • Valproate semisodique [French]
  • Valproate semisodium
  • Valproato semisodico [Spanish]
  • Valproatum seminatricum [Latin]
  • n-DPA
  • n-Dipropylacetic acid
  • valproate
  • valproic acid
Trade Names
  • Alti-Valproic
  • Avugane
  • Baceca
  • Convulex
  • Delepsine
  • Depacon
  • Depakene
  • Depakine
  • Depakote
  • Deproic
  • Dom-Valproic
  • Epilex
  • Epilim
  • Epival
  • Ergenyl
  • Med Valproic
  • Mylproin
  • Novo-Valproic
  • Nu-Valproic
  • PMS-Valproic Acid
  • Penta-Valproic
  • Sprinkle
  • Stavzor
  • Valcote
  • Valparin
  • Valproic acid USP
  • Valproic acid USP24
Brand Mixture Names

PharmGKB Accession Id:
PA451846

Description

A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage dependent sodium channels. Typically supplied in the sodium salt form (76584-70-8). Valproic Acid is also a histone deacetylase inhibitor and is under investigation for treatment of HIV and various cancers.

Source: Drug Bank

Indication

For treatment and management of seizure disorders, mania, and prophylactic treatment of migraine headache.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Valproic Acid binds to and inhibits GABA transaminase. The drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. It is also a histone deacetylase inhibitor.

Source: Drug Bank

Pharmacology

Valproic Acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome. Valproic Acid is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain. Valproic Acid dissociates to the valproate ion in the gastrointestinal tract. Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Do not take with milk.|Take with food.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Valproic Acid is metabolized almost entirely by the liver. In adult patients on monotherapy, 30-50% of an administered dose appears in urine as a glucuronide conjugate. Mitochondrial beta-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose. Usually, less than 15-20% of the dose is eliminated by other oxidative mechanisms. Less than 3% of an administered dose is excreted unchanged in urine.

Source: Drug Bank

Protein Binding

Concentration-dependent, from 90% at 40 µg/mL to 81.5% at 130 µg/mL.

Source: Drug Bank

Absorption

Rapid absorption from gastrointestinal tract.

Source: Drug Bank

Half-Life

9-16 hours

Source: Drug Bank

Toxicity

Oral, mouse: LD 50 = 1098 mg/kg; Oral, rat: LD 50 = 670 mg/kg. Symptoms of overdose may include coma, extreme drowsiness, and heart problems.

Source: Drug Bank

Clearance

Source: Drug Bank

Route of Elimination

Valproate is metabolized almost entirely by the liver. Less than 3% of an administered dose is excreted unchanged in urine. Mitochondrial ß-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose.

Source: Drug Bank

Volume of Distribution

Source: Drug Bank

Chemical Properties

Chemical Formula

C8H16O2

Source: Drug Bank

Isomeric SMILES

CCCC(CCC)C(=O)O

Source: OpenEye

Canonical SMILES

CCCC(CCC)C(O)=O

Source: Drug Bank

Average Molecular Weight

144.2114

Source: Drug Bank

Monoisotopic Molecular Weight

144.115029756

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Valproic Acid Pathway, Pharmacodynamics
    Graphic representation of the candidate genes involved in valproic acid pharmacodynamics.
  1. Valproic Acid Pathway, Pharmacokinetics
    Graphic representation of the candidate genes involved in valproic acid pharmacokinetics.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ABAT (source: Drug Bank)
ACADSB (source: Drug Bank)
HDAC9 (source: Drug Bank)

Drug Interactions

Drug Description
valproic acid The salicylate increases the effect of valproic acid (source: Drug Bank)
valproic acid Decreases the effect of valproic acid (source: Drug Bank)
valproic acid Valproic acid increases the effect of nimodipine (source: Drug Bank)
clarithromycin The macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Clarithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
erythromycin The macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Erythromycin is initiated, discontinued or dose changed. (source: Drug Bank)
felbamate Felbamate, a CYP2C19 inhibitor, may decrease the metabolism of Valproic acid, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Felbamate is initiated, discontinued or dose changed. (source: Drug Bank)
lamotrigine Valproic acid may increase the adverse effects of Lamotrigine by increasing Lamotrigine serum concentration. The Lamotrigine dose should be reduced by 50% during concomitant therapy. Monitor for changes in Lamotrigine therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed. (source: Drug Bank)
lorazepam Valproic acid may increase the serum concentration of Lorazepam by reducing Lorazepam metabolism. The Lorazepam dose should be reduced by 50% during concomitant therapy. Monitor for increased Lorazepam effects and toxicity. (source: Drug Bank)
rifampin Rifampin may reduce the serum concentration of Valproic acid by increasing Valproic acid metabolism. Valproic acid dose adjustments may be required during concomitant therapy. Monitor Valproic acid serum concentrations, efficacy and toxicity if Rifampin is initiated, discontinued or dose changed. (source: Drug Bank)
telithromycin The macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to valproic acid: 67

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Use of magnetic resonance imaging in pharmacogenomics. British journal of clinical pharmacology. 2014. Viviani Roberto, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Gene-wide tagging study of the effects of common genetic polymorphisms in the alpha subunits of the GABAA receptor on epilepsy treatment response. Pharmacogenomics. 2013. Hung Chin-Chuan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
GABRG2, rs211037 is associated with epilepsy susceptibility, but not with antiepileptic drug resistance and febrile seizures. Pharmacogenetics and genomics. 2013. Balan Shabeesh, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013. Cheung Ying-Kit, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs: a multicenter cohort study and meta-analysis. Pharmacogenomics. 2013. Haerian Batoul Sadat, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics of bipolar disorder. Pharmacogenomics. 2013. Severino Giovanni, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Valproic acid pathway: pharmacokinetics and pharmacodynamics. Pharmacogenetics and genomics. 2013. Ghodke-Puranik Yogita, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Neurotrophic Tyrosine Kinase Receptor Type 2 (NTRK2) Gene Associated with Treatment Response to Mood Stabilizers in Patients with Bipolar I Disorder. Journal of molecular neuroscience : MN. 2013. Wang Zuowei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for cytochrome P-450, family 2, subfamily A, polypeptide 6. Pharmacogenetics and genomics. 2012. McDonagh Ellen M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effects of UGT1A6, UGT2B7, and CYP2C9 genotypes on plasma concentrations of valproic acid in Chinese children with epilepsy. Drug metabolism and pharmacokinetics. 2012. Guo Yingjie, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Lack of association between ABCC2 gene variants and treatment response in epilepsy. Pharmacogenomics. 2012. Hilger Eva, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A genomic approach to predict synergistic combinations for breast cancer treatment. The pharmacogenomics journal. 2011. Soldi R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Possible role of CYP2C9 & CYP2C19 single nucleotide polymorphisms in drug refractory epilepsy. The Indian journal of medical research. 2011. Lakhan Ram, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association of genetic variants in six candidate genes with valproic acid therapy optimization. Pharmacogenomics. 2011. Hung Chin-Chuan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of valproic acid on organic acid metabolism in children: a metabolic profiling study. Clinical pharmacology and therapeutics. 2011. Price K E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population. Indian journal of human genetics. 2011. Kumari Ritu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Perspectives on Epigenetics and Its Relevance to Adverse Drug Reactions. Clinical pharmacology and therapeutics. 2011. Kacevska M, et al. PubMed
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Pharmacogenetics of drug-induced birth defects: what is known so far?. Pharmacogenomics. 2011. Wilffert Bob, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gene-wide tagging study of the association between ABCC2, ABCC5 and ABCG2 genetic polymorphisms and multidrug resistance in epilepsy. Pharmacogenomics. 2011. Kwan Patrick, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction networks of lithium and valproate molecular targets reveal a striking enrichment of apoptosis functional clusters and neurotrophin signaling. The pharmacogenomics journal. 2011. Gupta A, et al. PubMed
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New insights on the mechanisms of valproate-induced hyperammonemia: Inhibition of hepatic N-acetylglutamate synthase activity by valproyl-Coa. Journal of hepatology. 2010. Aires Cátia C P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymerase gamma gene POLG determines the risk of sodium valproate-induced liver toxicity. Hepatology (Baltimore, Md.). 2010. Stewart Joanna D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genetic polymorphisms in sex hormone metabolizing genes and drug response in women with epilepsy. Pharmacogenomics. 2010. Grover Sandeep, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identifying genomic and developmental causes of adverse drug reactions in children. Pharmacogenomics. 2010. Becker Mara L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Effect of CPS14217C>A genotype on valproic-acid-induced hyperammonemia. Pediatrics international : official journal of the Japan Pediatric Society. 2010. Yagi Mariko, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Transporter hypothesis of drug-resistant epilepsy: challenges for pharmacogenetic approaches. Pharmacogenomics. 2010. Potschka Heidrun. PubMed
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Influence of CYP2C9 polymorphism on metabolism of valproate and its hepatotoxin metabolite in Iranian patients. Toxicology mechanisms and methods. 2010. Amini-Shirazi Noushin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Absence of a general association between ABCB1 genetic variants and response to antiepileptic drugs in epilepsy patients. Biochimie. 2010. Grover Sandeep, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic profile of patients with epilepsy on first-line antiepileptic drugs and potential directions for personalized treatment. Pharmacogenomics. 2010. Grover Sandeep, et al. PubMed
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. PubMed
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Key factors in the discovery and development of new antiepileptic drugs. Nature reviews. Drug discovery. 2010. Bialer Meir, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling. European journal of clinical pharmacology. 2009. Jiang Dechun, et al. PubMed
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Molecular and therapeutic potential and toxicity of valproic acid. Journal of biomedicine & biotechnology. 2010. Chateauvieux Sébastien, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. Journal of hematology & oncology. 2010. Tan Jiahuai, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Structure, function, regulation and polymorphism of human cytochrome P450 2A6. Current drug metabolism. 2009. Di Yuan Ming, et al. PubMed
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Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population. British journal of clinical pharmacology. 2009. Lakhan Ram, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Valproic acid at therapeutic plasma levels may increase 5-azacytidine efficacy in higher risk myelodysplastic syndromes. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Voso Maria Teresa, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Preliminary evidence on the association between XBP1-116C/G polymorphism and response to prophylactic treatment with valproate in bipolar disorders. Psychiatry research. 2009. Kim Byungsu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Hauswald Stefanie, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Epilepsy pharmacogenetics. Pharmacogenomics. 2009. Kasperavici¿te Dalia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gene-wide tagging study of association between ABCB1 polymorphisms and multidrug resistance in epilepsy in Han Chinese. Pharmacogenomics. 2009. Kwan Patrick, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association of MDR1 C3435T polymorphism with bipolar disorder in patients treated with valproic acid. Molecular biology reports. 2009. Turgut Gunfer, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
No association of ABCB1 polymorphisms with drug-refractory epilepsy in a north Indian population. Epilepsy & behavior : E&B. 2009. Lakhan R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Modest reactivation of the mutant FMR1 gene by valproic acid is accompanied by histone modifications but not DNA demethylation. Pharmacogenetics and genomics. 2008. Tabolacci Elisabetta, et al. PubMed
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Machine learning methods and docking for predicting human pregnane X receptor activation. Chemical research in toxicology. 2008. Khandelwal Akash, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenetics and genomics. 2008. Hung Chin-Chuan, et al. PubMed
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Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clinical pharmacology and therapeutics. 2008. Chung J-Y, et al. PubMed
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Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways. Drug metabolism and disposition: the biological fate of chemicals. 2007. Cerveny Lukas, et al. PubMed
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Inhibitory effect of valproic acid on cytochrome P450 2C9 activity in epilepsy patients. Basic & clinical pharmacology & toxicology. 2007. Gunes Arzu, et al. PubMed
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Contribution of CYP2C9, CYP2A6, and CYP2B6 to valproic acid metabolism in hepatic microsomes from individuals with the CYP2C9*1/*1 genotype. Toxicological sciences : an official journal of the Society of Toxicology. 2006. Kiang Tony K L, et al. PubMed
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Mitochondrial DNA polymerase-gamma and human disease. Human molecular genetics. 2006. Hudson Gavin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate. Annals of neurology. 2006. Brichta Lars, et al. PubMed
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ABCB1 polymorphisms influence the response to antiepileptic drugs in Japanese epilepsy patients. Pharmacogenomics. 2006. Seo Takayuki, et al. PubMed
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Defining the clinical role of pharmacogenetics in antiepileptic drug therapy. The pharmacogenomics journal. 2006. Dlugos D J, et al. PubMed
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Idiosyncratic drug hepatotoxicity. Nature reviews. Drug discovery. 2005. Kaplowitz Neil. PubMed
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UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). The Journal of pharmacology and experimental therapeutics. 2005. Krishnaswamy Soundararajan, et al. PubMed
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The effect of valproic acid on drug and steroid glucuronidation by expressed human UDP-glucuronosyltransferases. Biochemical pharmacology. 2003. Ethell Brian T, et al. PubMed
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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. PubMed
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Med-psych drug-drug interactions update. Psychosomatics. 2002. Armstrong Scott C, et al. PubMed
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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. PubMed
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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. PubMed
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Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia. 1997. Rosenfeld W E, et al. PubMed
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Valproic acid-carbamazepine interaction: is valproic acid a selective inhibitor of epoxide hydrolase?. Therapeutic drug monitoring. 1995. Svinarov D A, et al. PubMed
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The enzymatic basis for the metabolism and inhibitory effects of valproic acid: dehydrogenation of valproyl-CoA by 2-methyl-branched-chain acyl-CoA dehydrogenase. Biochimica et biophysica acta. 1990. Ito M, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0121-0675-16
DrugBank:
DB00313
ChEBI:
9926
KEGG Compound:
C07185
KEGG Drug:
D00399
PubChem Compound:
3121
PubChem Substance:
46505925
Drugs Product Database (DPD):
2260654
ChemSpider:
3009
Therapeutic Targets Database:
DNC001659
FDA Drug Label at DailyMed:
7d5cb52e-37dd-4dfa-a6f4-09f9548846c6

Clinical Trials

These are trials that mention valproic acid and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.