Gender differences in the oral pharmacokinetics of Fluconazole

Background and objective: Fluconazole is a triazole derivative widely used for the treatment of mycoses. It has been established that several factors are able to modify its pharmacokinetics, including the bodyweight of the patient; however, there is controversy about the influence of gender on the pharmacokinetics of fluconazole. In order to clarify this controversy we decided to evaluate the pharmacokinetics of fluconazole in males and females. Methods: Fifty-nine subjects (26 males and 33 females) were enrolled in this study. Volunteers received an oral dose of fluconazole 100mg under fasting conditions and blood samples were collected at selected times over a period of 96 hours. Plasma was obtained and analysed by a high-performance liquid chromatography method. Results: The plasma fluconazole concentrations obtained in women were higher than those obtained in men. This was reflected in differences in most pharmaco-kinetic parameters. However, when parameters were normalised according to the bodyweight of subjects, differences were reduced, indicating that this factor plays a role in the differences observed. Notwithstanding, differences in other parameters, such as normalised maximum plasma concentration, time to reach maximum plasma concentration, volume of distribution and half-life, remained. Conclusion: Fluconazole pharmacokinetics are influenced by both bodyweight and gender, most likely because of differences in total body water between males and females. Although the clinical impact on efficacy and safety of the pharmaco-kinetic differences observed in this study was not established, it is desirable that fluconazole dosage regimens take into account both the gender and the bodyweight of the patient.