Dorado Pedro, Berecz Roland, Cáceres Macarena C, Conzález Idilio, Llerena Adrián
Department of Pharmacology and Psychiatry, Faculty of Medicine, University of Extremadura, Badajoz, Spain.
Eur J Drug Metab Pharmacokinet. 2003 Jul-Sep;28(3):213-5. doi: 10.1007/BF03190487.
Diclofenac has been used for the evaluation of CYP2C9 activity in vitro as well as in vivo with varying results. The present study was aimed at evaluating the reproducibility of the urinary diclofenac/4'-OH diclofenac ratio among different CYP2C9 genotypes in healthy volunteers. The study of CYP2C9 genotypes in the family of a CYP2C93/3 subject is also reported. The urinary diclofenac/4'-OH diclofenac ratio was determined on two occasions within a period of 9-12 months, and was found to be correlated (r = 0.83, p < 0.05). The mean (+/- SD) of diclofenac/4'-OH diclofenac ratio was 1.5 times higher among subjects carrying CYP2C93 allele (CYP2C91/3 and CYP2C92/3 genotypes) (0.91 +/- 0.28), compared to CYP2C91/1 subjects (0.60 +/- 0.11). The results show that the urinary diclofenac/4'-OH diclofenac ratio might be used to study CYP2C9 in humans. The data agree with previous studies showing that the CYP2C93 allelic variant seems to cause a decreased CYP2C9 hydroxylation capacity.
双氯芬酸已被用于体外和体内评估CYP2C9活性，结果各异。本研究旨在评估健康志愿者中不同CYP2C9基因型之间尿双氯芬酸/4'-羟基双氯芬酸比值的可重复性。还报告了对一名CYP2C93/3受试者家族中CYP2C9基因型的研究。在9至12个月内分两次测定尿双氯芬酸/4'-羟基双氯芬酸比值，发现两者具有相关性（r = 0.83，p < 0.05）。携带CYP2C93等位基因（CYP2C91/3和CYP2C92/3基因型）的受试者中双氯芬酸/4'-羟基双氯芬酸比值的平均值（±标准差）比CYP2C91/1受试者（0.60±0.11）高1.5倍（0.91±0.28）。结果表明，尿双氯芬酸/4'-羟基双氯芬酸比值可能用于研究人类的CYP2C9。这些数据与先前的研究一致，表明CYP2C93等位基因变体似乎会导致CYP2C9羟化能力下降。
