Oral Pharmacokinetics of Felodipine in Mexican Healthy Volunteers: Evidence for Interethnic Differences

Felodipine is an inhibitor of the calcium entry channels which is indicated for hypertension and chest angina disorders. The oxidative biotransformation of felodipine is mediated primarily by CYP3A4. Interethnic differences in the pharmacokinetics of drugs metabolized by CYP3A4 have been reported, being Mexicans a population endowed reduced metabolism by this pathway. Due to the relevance of this enzyme in our population and the fact that until our knowledge no pharmacokinetic data of felodipine in Mexican population is available, the purpose of this study was to evaluate the oral pharmacokinetics of felodipine in Mexican healthy subjects and compare with those reported in Caucasians subjects. Thirty volunteers received an oral dose of 5 mg of felodipine after a fasting period of 10 h. Plasma levels were determined by a high performance liquid chromatography method coupled to tandem mass spectrometry. Pharmacokinetic parameters were obtained by non-compartmental techniques. The results obtained (Mean+/-SEM) were: maximal concentration (C-max) 4.63+/-0.40 nmol L-1, time to reach this concentration (t(max)) 3.63+/-0.28 h, area under the plasma concentration against time curve (AUC) 59.53+/-6.44 nmol h L-1 and half-life (t(1/2)) 16.62+/-1.25 h. The results obtained were compared with those values reported in other populations under similar conditions. The bioavailability of felodipine observed in this study was higher than that reported for Caucasians. Since felodipine is eliminated primarily by CYP3A4 metabolism, our data provide an additional evidence of reduced activity of this enzymatic pathway in Mexican population.