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Influences of CYP2C9 genotype and fluvastatin on pharmacokinetics and pharmacodynamics of nateglinide
Author(s) -
Uchida S.,
Nishio S.,
Li X. D.,
Ito T.,
Morita H.,
Nakamura H.,
Yamada H.,
Watanabe H.,
Ohashi K.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.172
Subject(s) - pharmacodynamics , pharmacokinetics , fluvastatin , cyp2c9 , pharmacology , nateglinide , medicine , clinical pharmacology , genotype , biology , genetics , simvastatin , endocrinology , type 2 diabetes , diabetes mellitus , gene
Aims The aim of this study was to clarify the influences of CYP2C9 genotype and co‐administration of fluvastatin on pharmacokinetics and pharmacodynamics of nateglinide. Methods In randomized cross‐over study with two phases, 14 healthy volunteers received fluvastatin (30 mg/day) or placebo for 7 days. On day 8, after an overnight fasting, nateglinide (120 mg) was administered with fluvastatin or placebo, and 75g glucose was given directly after nateglinide intake. Concentrations of nateglinide, insulin and glucose in plasma were determined. Results AUC of nateglinide in CYP2C9*1/*3 and CYP2C9*3/*3 were 1.4 and 2.0 fold higher than that in CYP2C9*1/*1 , respectively. The difference was significant between CYP2C9*1/*1 and CYP2C9*1/*3 . Fluvastatin significantly increased AUC of nateglinide by 18 % in all subjects. There were no significant differences in glucose and insulin levels after the administration of nateglinide both among CYP2C9 genotypes and between the administrations of fluvastatin and placebo. Conclusion These results suggested that both CYP2C9*3 allele and fluvastatin influence the pharmacokinetics of nateglinide. Clinical Pharmacology & Therapeutics (2005) 77 , P74–P74; doi: 10.1016/j.clpt.2004.12.172