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Effects of CYP2C9 genetic polymorphism on the pharmacokinetics and pharmacodynamics of glipizide in healthy Korean subjects
Author(s) -
BAE JUNGWOO,
KIM NAMTAE,
CHOI CHANGIK,
KIM MIJEONG,
JANG CHOONGON,
LEE SEOKYONG
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb77-d
Subject(s) - glipizide , cyp2c9 , pharmacokinetics , pharmacodynamics , pharmacology , genotype , medicine , genotyping , endocrinology , insulin , chemistry , metabolism , biochemistry , cytochrome p450 , gene
Glipizide is a second‐generation sulfonylurea antidiabetic agent with high potency. Our objective was to investigate the effects of CYP2C9∗3 and ∗13 alleles on the pharmacokinetics (PK) and pharmacodymamics (PD) of glipizide. 340 healthy Korean volunteers were recruited for genotyping of CYP2C9 , and 20 subjects of them were selected for PK and PD study of glipizide. There were 9 subjects with CYP2C9∗1/∗1 genotype, 8 subjects with CYP2C9∗1/∗3 genotype and 3 subjects with CYP2C9∗1/∗13 genotype. A single oral dose of 5 mg glipizide was administered to each volunteers, and plasma concentration of glipizide was measured by HPLC. Plasma concentrations of glucose and insulin were also measured by glucose oxidase method and radioimmunoassay, respectively. Three genotypes of CYP2C9 ( CYP2C9∗1/∗1 , ∗1/∗3 and ∗1/∗13 ) were detected in 340 Korean volunteers. The pharmacokinetics of glipizide were significantly different dependent on CYP2C9 genotype. In subjects with the CYP2C9∗1/∗3 and CYP2C9∗1/∗13 , the mean AUC 0‐inf were 135.2% (P < 0.01) and 156.1% (P < 0.01) of the respective value in those with the CYP2C9∗1/∗13 . However, CYP2C9∗3 and ∗13 alleles didn¡ ¯ t significantly affected the effects of glipizide on plasma concentration of glucose and insulin. In conclusion, the defective CYP2C9∗3 and CYP2C9∗13 alleles significantly increased the AUC 0‐inf of glipizide, but they did not elicit the significant changes in PD of glipizide. (This study was supported by the 2007 Research fund from KFDA