Comparison of the oral pharmacokinetics of fluconazole and itraconazole in Mexicans.

Abstract

Fluconazole and itraconazole are antimycotics widely used in Mexico. However, limited information about their pharmacokinetics is available. It has been reported that physicochemical characteristics of these compounds are disparate, leading to different pharmacokinetic profiles. Moreover, it has been suggested that pharmacokinetics of some drugs may vary in Mexicans when compared with Caucasians due to reduced metabolism by CYP3A4. Based on these distinctions, it is important to carry out local studies in order to establish dosage regimens according the characteristics of each population. The purpose of this study was to compare the oral pharmacokinetics of fluconazole and itraconazole in Mexicans and to compare our results with those reported in other populations. Two groups of 16 subjects volunteered for this study that was approved by the Institutional Research and Ethics Committees. All subjects gave written informed consent for participation. After an overnight fast, volunteers received an oral dose of 100 mg fluconazole or itraconazole and blood samples were obtained at selected times over 96 hr. Plasma was obtained and analyzed by HPLC and pharmacokinetic parameters were obtained. As expected, fluconazole plasma levels were higher than itraconazole due to a lower volume of distribution. Additionally, less variability was observed for fluconazole. When data obtained in Mexicans was compared with those obtained in other populations, no differences were observed, suggesting that there are not interethnic differences in the pharmacokinetics of fluconazole and itraconazole.