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Background/Aims The purpose of this study was to investigate the effect of the CYP2C8 genetic polymorphisms CYP2C8*2, CYP2C8*3, and CYP2C8*4 on the pharmacokinetics of rosiglitazone, a PPARγ agonist and CYP2C8 substrate. Methods This single dose pharmacokinetics study involved thirty-eight healthy subjects with the following CYP2C8 genotypes: CYP2C8*1/*1 (n= 14), *1/*2 (n= 5), *1/*3 (n= 11), *1/*4 (n= 6), *2/*2 (n= 1), and *3/*3 (n= 1). Subjects were administered a single dose of rosiglitazone 8 mg. Rosiglitazone concentrations were determined by HPLC and noncompartmental pharmacokinetic parameters were compared between wild type and heterozygous genotype groups. Results The pharmacokinetics of rosiglitazone did not differ between CYP2C8 homozygous wild type and heterozygous individuals. The mean AUC was 3161±625, 3290±866, 2928±519, and 3230±658, μg×h/L in the *1/*1, *1/*2, *1/*3, and *1/*4 genotype groups, respectively. The subject with the CYP2C8*3/*3 genotype had the second lowest rosiglitazone AUC. Conclusions The pharmacokinetics of rosiglitazone were not different in individuals carrying a single variant CYP2C8 allele, as the pharmacokinetic parameters of rosiglitazone did not differ between heterozygous and homozygous wild type individuals. Further study is needed to determine whether homozygous carriers of the CYP2C8*2 and CYP2C8*3 alleles have altered rosiglitazone pharmacokinetics. Clinical Pharmacology & Therapeutics (2005) 77, P36–P36; doi: 10.1016/j.clpt.2004.12.029 |
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