title: Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide.
abstract: OBJECTIVE
  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.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: He
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Han
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Fan
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Tan
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Zhang
authors.forename: Bang-Ning
authors.initials: BN
authors.lastname: Yu
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Dong-Li
authors.initials: DL
authors.lastname: Hu
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000328:Adult; D003510:Cyclohexanes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D000077715:Nateglinide; D027361:Organic Anion Transporters / Q000235:genetics*; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D000077715:Nateglinide; D010649:Phenylalanine