Document Detail


Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide.
MedLine Citation:
PMID:  16796707     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Nateglinide is a meglitinide analogue with antidiabetic action. A recent study showed that SLCO1B1 (which codes the OATP1B1 gene, also known as OATP-C, OATP2) is a major determinant which markedly affects the pharmacokinetics of repaglinide. Our objective was to assess the association between single nucleotide polymorphisms (SNPs) of SLCO1B1 and the pharmacokinetics of nateglinide. METHODS: Seventeen healthy volunteers with different SLCO1B1 genotypes (11 with 521TT, four with 521TC and two with 521CC) were enrolled in this study. Each was given a single oral dose of 90 mg nateglinide. Plasma concentrations of nateglinide were measured up to 8 h by HPLC. RESULTS: The C(max) and AUC(0,infinity) of nateglinide were 83% (P = 0.002) and 82% (P = 0.001) higher in the SLCO1B1521TC subjects (n = 4), and 76% (P = 0.016) and 108% (P = 0.001) higher in the SLCO1B1521CC subjects (n = 2) than in the SLCO1B1521TT subjects (n = 11), respectively. The t(1/2) of nateglinide in SLCO1B1521CC subjects was 78% longer than that in 521TT subjects (P = 0.036). The difference in t(max) values among the three genotypic groups was not statistically significant. CONCLUSIONS: Our results suggest that OATP1B1-mediated hepatic uptake of nateglinide may be the prior step for its metabolism and elimination. SLCO1B1521T > C SNP might play an important role in the pharmacokinetics of nateglinide.
Authors:
Wei Zhang; Yi-Jing He; Chun-Ting Han; Zhao-Qian Liu; Qing Li; Lan Fan; Zhi-Rong Tan; Wei-Xia Zhang; Bang-Ning Yu; Dan Wang; Dong-Li Hu; Hong-Hao Zhou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-23
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  62     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-25     Completed Date:  2007-03-29     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  567-72     Citation Subset:  IM    
Affiliation:
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, PR China.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cyclohexanes / administration & dosage,  pharmacokinetics,  therapeutic use*
Diabetes Mellitus / drug therapy,  genetics*
Humans
Hypoglycemic Agents / therapeutic use*
Male
Organic Anion Transporters / genetics*
Phenylalanine / administration & dosage,  analogs & derivatives*,  pharmacokinetics,  therapeutic use
Polymorphism, Single Nucleotide / genetics*
Chemical
Reg. No./Substance:
0/Cyclohexanes; 0/Hypoglycemic Agents; 0/Organic Anion Transporters; 0/SLCO1B1 protein, human; 105816-04-4/nateglinide; 63-91-2/Phenylalanine
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