Parametric and nonparametric population pharmacokinetic analysis of fluconazole in critically ill patients and dosing simulations for

Large pharmacokinetic (PK) variability of fluconazole has been reported in critically ill patients, but the implications for fluconazole dosing remain unclear. The objectives of this study were to evaluate the population PK of fluconazole and identify appropriate dosage regimens by simulations. This was a retrospective analysis of fluconazole PK data from patients hospitalized in critical care and infectious disease departments. Both parametric and nonparametric population approaches were used. Various loading and maintenance fluconazole doses were evaluated by simulations, with computation of the probabilities of PK/pharmacodynamic (PD) target attainment (PTA) and cumulative fractions of response (CFR) based on international and local minimum inhibitory concentration (MIC) distributions of