Frequency of CYP2C9 variant alleles, including CYP2C9*13 in a Korean population and effect on glimepiride pharmacokinetics

Title
Frequency of CYP2C9 variant alleles, including CYP2C9*13 in a Korean population and effect on glimepiride pharmacokinetics
Author(s)
임미선Lee HW[Lee HW]Lee J[Lee J]Jegal MY[Jegal MY]Kim DW[Kim DW]Lee WK[Lee WK]Jang IJ[Jang IJ]Shin JG[Shin JG]Yoon YR[Yoon YR]
Keywords
CYTOCHROME P4502C9 POLYMORPHISMS; GENETIC POLYMORPHISMS; PYROSEQUENCING METHOD; MASS-SPECTROMETRY; DEFECTIVE ALLELES; MUTANT ALLELES; JAPANESE; CHINESE; METABOLISM; EXTRACTION
Issue Date
201202
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, v.37, no.1, pp.105 - 111
Abstract
What is known and Objective: Cytochrome P450 (CYP) 2C9 is a clinically important enzyme involved in the metabolism of many drugs commonly used in humans. Of several allelic variants known to affect the catalytic activity of the CYP2C9 enzyme, the frequencies of the CYP2C9*3 and CYP2C9*13 alleles in the Korean population have been reported as 1.1% and 0.6%, respectively. Our objective was to re-evaluate the frequencies of CYP2C9 allelic variants in the Korean population, including the CYP2C9*13 allele by pyrosequencing, and to investigate the pharmacokinetics of glimepiride in relation to CYP2C9 genotypes, including CYP2C9*3/*3. Methods: 295 subjects were genotyped for CYP2C9*2 and CYP2C9*3 using the TaqMan procedure, and for CYP2C9*13 using pyrosequencing. These data were combined with our previously reported data to assess the CYP2C9 allele and genotype frequencies in 869 Korean subjects. Data from 24 of the 295 genotyped subjects (22 CYP2C9*1/*1 homozygotes, one CYP2C9*1/*3 heterozygote and one CYP2C9*3/*3 homozygote) who had participated in a bioequivalence study were analysed retrospectively to examine the effects of CYP2C9 genotype on glimepiride pharmacokinetics. Results: The frequencies of the CYP2C9*1/*3, *3/*3, and *1/*13 genotypes in the study population (n = 295) were 0.081 (n = 24), 0.010 (n = 3) and 0.003 (n = 1), respectively. In the 869 subjects from the combined studies, allele frequencies for CYP2C9*3 and CYP2C9*13 were 0.025 (95% CI: 0.018, 0.033) and 0 002 (95% CI: 0.000, 0.010), respectively. Relative to CYP2C9*1 homozygotes, the one CYP2C9*3 homozygous subject was found to have a higher AUC(0-infinity) value (490% of the reference value) and a lower oral clearance rate (18% of the reference). What is new and Conclusion: This study is the first examination of CYP2C9*3 homozygotes in the Korean population. Our data on the one subject with this genotype suggest that CYP2C9*3/*3 momozygotes have lower clearance of glimepiride and are exposed to higher levels of the drug than wildtype homozygotes. Although we identified a subject with the CYP2C9*13 allele using a new pyrosequencing assay, we were unfortunately unable to investigate its effects on glimepiride pharmacokinetics.
URI
http://hdl.handle.net/YU.REPOSITORY/29826http://dx.doi.org/10.1111/j.1365-2710.2010.01238.x
ISSN
0269-4727
Appears in Collections:
약학대학 > 약학부 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE