Evaluation of Dosages Regimen of Fluconazole in Patients of Candidemia with Gender by PK/PD and Mote Carlo Simulation

Abstract

Candidemia is one of the four most common nosocomial blood infections and is the most common hospital-acquired fungemia in a recent multi-institutional study from the US. The mortality of Candidemia can be up to 50%. Fluconazole is a triazole derivative widely used for the treatment of invasive candidiasis. It was recommended as first-line drugs for the treatment and prevention of mycoses. In our study, we aimed to optimise the dosage of fluconazole with gender against Candida spp. based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of fluconazole and the MIC distribution of Candida spp. on fluconazole. We decided to evaluate the gender between males and females with the pharmacokinetics of fluconazole. Using probability of target attainment (PTA) and cumulative fraction of response (CFR) as indexes, crystal ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage regimens of different males and females. For C. albicans, C. tropicalis and C. lusitaniae, when doses of regimen are 100 mg IV, 200 mg IV and MIC was lower than 1 g/ml, PTA was higher than 90%. For C. tropicalis, each dosing regimen and MIC was less than 2 g/ml. PTA was higher than 90%. As C. glabrata, C. parapsilosis, C. krusei, C. guilliermondii for PTA with more than 90%, MIC of fluconazole 200 mg were less than 32 g/ml, 64 g/ml and 64 g/ml, respectively. For the different dosage regimens 100 mg IV and 200 mg IV of fluconazole for Candida spp., it is desirable that fluconazole dosage regimens take into account both the gender of the patient.