Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics
| Autor: | Jung-in Park, Hye-kyoung Bang, Bo-hye Kim, Ji-hey Ha, Hae-deun Kim, Myeon-Woo Chung, Mi-Jeong Kim, Hee-Jung Shin, Byung-sung Kang, Young-Hoon Kim, Choon-Gon Jang, Hyun Joo Park, Seul-ki Keum, Chang-Ik Choi, Sung-gon Oh, Seok-Yong Lee, Da-hee Oh, Jung-Woo Bae, Han-Sung Na |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype Tetrazoles Gastroenterology Losartan Young Adult Asian People Gene Frequency Pharmacokinetics Polymorphism (computer science) Internal medicine medicine Humans Pharmacology (medical) CYP2C9 Allele frequency Alleles Antihypertensive Agents Active metabolite Cytochrome P-450 CYP2C9 Pharmacology Traditional medicine business.industry Imidazoles General Medicine Confidence interval Original Article Aryl Hydrocarbon Hydroxylases business medicine.drug |
| Zdroj: | Acta Pharmacologica Sinica. 32:1303-1308 |
| ISSN: | 1745-7254 1671-4083 |
| DOI: | 10.1038/aps.2011.100 |
| Popis: | CYP2C9 enzyme metabolizes numerous clinically important drugs. The aim of this study is to investigate the frequencies of CYP2C9 genotypes and the effects of selected alleles on losartan pharmacokinetics in a large sample of the Korean population.The CYP2C9 gene was genotyped in 1796 healthy Korean subjects. CYP2C9 alleles (CYP2C9*1, *2, *3 and *13 alleles) were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and direct sequencing assay. The enzymatic activity of each CYP2C9 genotype was evaluated using losartan as the substrate.The frequencies of CYP2C9*1, *3 and *13 allele were 0.952 (95% confidence interval 0.945-0.959), 0.044 (95% CI 0.037-0.051) and 0.005 (95% CI 0.003-0.007), respectively. The frequencies of the CYP2C9*1/*1, *1/*3, *1/*13 and *3/*3 genotypes were 0.904 (95% CI 0.890-0.918), 0.085 (95% CI 0.072-0.098), 0.009 (95% CI 0.005-0.013) and 0.001 (95% CI 0.000-0.002), respectively. In the pharmacokinetics studies, the AUC(0-∞) of losartan in CYP2C9*3/*3 subjects was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC(0-∞) of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subjects was only 12% of that in CYP2C9*1/*1 subjects.The results confirmed the frequencies of CYP2C9 genotypes in a large cohort of Koreans, and detected the CYP2C9*3/*3 genotype. CYP2C9*3/*3 subjects metabolized much less losartan into E-3174 than CYP2C9*1/*1 subjects. |
| Databáze: | OpenAIRE |
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