Drug/Small Molecule:
nateglinide

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PharmGKB contains no drug labels with pharmacogenomic information for this drug/small molecule. To report a drug label with PGx, click here.

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.

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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 CYP2C9 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *3 N/A N/A N/A
No VIP available CA VA
rs4149056 14091673T>C, 21331549T>C, 521T>C, 52422T>C, SLCO1B1*5, Val174Ala
T > C
Missense
Val174Ala
VIP No Clinical Annotations available No Variant Annotations available
rs776746 12083G>A, 219-237G>A, 321-1G>A, 37303382C>T, 581-237G>A, 689-1G>A, 99270539C>T, CYP3A5*1, CYP3A5*3, CYP3A5*3C, CYP3A5:6986A>G, g.6986A>G, intron 3 splicing defect, rs776746 A>G
C > T
Acceptor
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Nateglinide [INN]
  • SDZ-DJN 608
  • nateglinide
Trade Names
  • Fastic
  • Starlix
  • Starsis
Brand Mixture Names

PharmGKB Accession Id:
PA450600

Description

Nateglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to beta cells of the pancreas to stimulate insulin release. Nateglinide is an amino acid derivative that induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal. Approximately one month of therapy is required before a decrease in fasting blood glucose is seen. Meglitnides may have a neutral effect on weight or cause a slight increase in weight. The average weight gain caused by meglitinides appears to be lower than that caused by sulfonylureas and insulin and appears to occur only in those naïve to oral antidiabetic agents. Due to their mechanism of action, meglitinides may cause hypoglycemia although the risk is thought to be lower than that of sulfonylureas since their action is dependent on the presence of glucose. In addition to reducing postprandial and fasting blood glucose, meglitnides have been shown to decrease glycosylated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Meglitinides appear to be more effective at lowering postprandial blood glucose than metformin, sulfonylureas and thiazolidinediones. Nateglinide is extensively metabolized in the liver and excreted in urine (83%) and feces (10%). The major metabolites possess less activity than the parent compound. One minor metabolite, the isoprene, has the same potency as its parent compound.

Source: Drug Bank

Indication

For the treatment of non-insulin dependent-diabetes mellitus in conjunction with diet and exercise.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Nateglinide activity is dependent on the presence functioning beta cells and glucose. In contrast to sulfonylurea insulin secretatogogues, nateglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, nateglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of nateglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Nateglinide appears to be selective for pancreatic beta cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.

Source: Drug Bank

Pharmacology

Insulin secretion by pancreatic beta cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Nateglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.

Source: Drug Bank

Food Interaction

Take upto 30 minutes before meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic, via cytochrome P450 isoenzymes CYP2C9 (70%) and CYP3A4 (30%). Metabolism is via hydroxylation followed by glucuronidation. The major metabolites have less antidiabetic activity than nateglinide, but the isoprene minor metabolite has antidiabetic activity comparable to that of nateglinide.

Source: Drug Bank

Protein Binding

98% bound to serum proteins, primarily serum albumin and to a lesser extent alpha1 acid glycoprotein

Source: Drug Bank

Absorption

Rapidly absorbed following oral administration prior to a meal, absolute bioavailability is estimated to be approximately 73%. Peak plasma concentrations generally occur within 1 hour of oral administration. Onset of action is <20 minutes and the duration of action is approximately 4 hours.

Source: Drug Bank

Half-Life

1.5 hours

Source: Drug Bank

Toxicity

An overdose may result in an exaggerated glucose-lowering effect with the development of hypoglycemic symptoms.

Source: Drug Bank

Route of Elimination

Urine (83%) and feces (10%)

Source: Drug Bank

Volume of Distribution

10 liters in healthy subjects

Source: Drug Bank

Chemical Properties

Chemical Formula

C19H27NO3

Source: Drug Bank

Isomeric SMILES

CC([C@H]1CC[C@H](CC1)C(=O)N[C@H](C(=O)O)CC2=CC=CC=C2)C

Source: Drug Bank

CC(C)[C@H]1CCC[C@@H](C1)C(=O)N[C@H](CC1=CC=CC=C1)C(O)=O

Source: Drug Bank

Canonical SMILES

CC(C)C1CC[C@@H](CC1)C(=O)N[C@H]

Source: Drug Bank

Average Molecular Weight

317.4226

Source: Drug Bank

Monoisotopic Molecular Weight

317.199093735

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Anti-diabetic Drug Nateglinide Pathway, Pharmacokinetics
    Nateglinide metabolism and transport in liver cell
  1. Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics
    Representation of anti-diabetic drugs repaglinide, nateglinide and sulfonylurea effects on insulin secretion in pancreatic cells.

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
ABCC4 (source: Drug Bank)
ABCC8 (source: Drug Bank)
KCNJ1 (source: Drug Bank)
KCNJ11 (source: Drug Bank)
PPARG (source: Drug Bank)

Drug Interactions

Drug Description
glucosamine Possible hyperglycemia (source: Drug Bank)
somatropin recombinant Somatropin may antagonize the hypoglycemic effect of nateglinide. Monitor for changes in fasting and postprandial blood sugars. (source: Drug Bank)
nateglinide Telithromycin may reduce clearance of Nateglenide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Nateglenide if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
nateglinide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Nateglinide. Consider alternate therapy or monitor for changes in Nateglinide therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank)
nateglinide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Nateglinide. Consider alternate therapy or monitor for changes in Nateglinide therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank)
nateglinide Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nateglinide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nateglinide if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank)

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

May Treat
Contraindicated With

Publications related to nateglinide: 7

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Effect of CYP2C9 and SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of nateglinide in healthy Chinese male volunteers. European journal of clinical pharmacology. 2013. Cheng Yu, 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 CYP3A5. Pharmacogenetics and genomics. 2012. Lamba Jatinder, 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 the SLCO1B1*1B haplotype on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinide. Pharmacogenetics and genomics. 2008. Kalliokoski Annikka, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Different effects of SLCO1B1 polymorphism on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinide. Journal of clinical pharmacology. 2008. Kalliokoski Annikka, 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
Prediction of the metabolic interaction of nateglinide with other drugs based on in vitro studies. Drug metabolism and pharmacokinetics. 2007. Takanohashi Toshiyuki, 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
Pharmacogenetics of glucose-lowering drug treatment: a systematic review. Molecular diagnosis & therapy. 2007. Bozkurt Ozlem, 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
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. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0078-0351-05
DrugBank:
DB00731
ChEBI:
146727
KEGG Compound:
C12508
KEGG Drug:
D01111
PubChem Compound:
60026
PubChem Substance:
196417
Drugs Product Database (DPD):
2245439
Therapeutic Targets Database:
DAP000918
FDA Drug Label at DailyMed:
5cbda9bc-3c0d-4d75-a37a-994844680c8c

Clinical Trials

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

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