Pharmacogenetic relevance of the CYP2C9*3 allele in a tenoxicam bioequivalence study performed on Spaniards.

Author(s): Peiro AM, Novalbos J, Zapater P, Moreu R, Lopez-Rodriguez R, Rodriguez V, Abad-Santos F, Horga JF

Affiliation(s): Division of Pharmacology and Therapeutics, Instituto de Bioingenieria, Miguel Hernandez University, Campus de San Juan, San Juan de Alicante, Alicante, Spain.

Publication date & source: 2009-01, Pharmacol Res., 59(1):62-8. Epub 2008 Oct 17.

Publication type: Clinical Trial, Phase I; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

We performed a study to quantify CYP2C9 and CYP2C8 alleles influence on the variability observed in tenoxicam pharmacokinetic (PK) and implication in a bioequivalence study design performed on Spaniards. Eighteen healthy volunteers were included in an open, randomized, crossover, phase I bioequivalence study. Significant increases were found in CYP2C9*3 alleles vs. *1 and *2 in AUC(0-infinity) (median (min-max)): 256 (230-516) vs. 150 (100-268) and 169 (124-197) microg h/mL (p<0.01) and half-life time (t1/2) 102 (79-36) vs. 56 (45-94) and 64 (60-80)h (p<0.01). Non-significant differences were observed in C(max) 1.9 (1.8-2.9) vs. 2.4 (1.7-3.4), 2.5 (1.6-2.9) microg/mL or in according to CYP2C8 alleles presence. CYP2C9*3 allele is associated to a longer elimination time of tenoxicam. PK parameters calculated in bioequivalence studies (AUC(0-infinity), t1/2) may be influenced by the presence of CYP2C9*3 allele resulting in a high variability. Thus, bioequivalence studies of tenoxicam formulations should be designed considering genotype profile.