Pharmacokinetics of diclofenac in healthy controls with wild-type phenotype for CYP2C9 shows metabolism variability

Background

Cytochrome P450 2C9 (CYP2C9) is an important enzyme in the metabolism of many drugs, including NSAIDs, antidepressants and anticoagulants. In vitro and in vivo studies have demonstrated that CYP2C9 polymorphisms modify the activity of the enzyme and subsequently the metabolism of different drugs.

Objective

To characterize the diclofenac pharmacokinetics in healthy subjects with the wild type form of CYP2C9 genotype.

Methods

Twenty five healthy women were included in the study; a single dose of diclofenac (50 mg) was administered orally. Pharmacokinetic analyses at 12 different times were performed. DNA was extracted from peripheral blood and analyzed through direct sequencing. The CYP2C9*1/*1 allele was found in all subjects. Using the AUC 0-inf parameter, we classified the 25 volunteers as poor, intermediate and extensive metabolizer (2285.421/3217.442/4637.450, respectively). We detected statistical significant differences between the groups, especially between poor metabolizers versus intermediate and extensive metabolizers.

Conclusions

This data indicate that CYP2C9 is not the only enzyme responsible of the metabolism of diclofenac, so it is important to analyze other cytochromes and their variants potentially involved in the metabolism of this drug.