Reproducibility over time of the urinary diclofenac/4′-OH diclofenac ratio among differentCYP2C9 genotypes
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Diclofenac has been used for the evaluation of CYP2C9 activityin vitro as well asin vivo with varying results. The present study was aimed at evaluating the reproducibility of the urinary diclofenac/4′-OH diclofenac ratio among differentCYP2C9 genotypes in healthy volunteers. The study ofCYP2C9 genotypes in the family of aCYP2C9*3/*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 carryingCYP2C9*3 allele (CYP2C9*1/*3 andCYP2C9*2/*3 genotypes) (0.91±0.28), compared toCYP2C9*1/*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 theCYP2C9*3 allelic variant seems to cause a decreased CYP2C9 hydroxylation capacity.
KeywordsCYP2C9 diclofenac losartan cytochrome P450
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