RESUMEN
We investigated covariates of pharmacokinetics of micafungin in critically ill patients. After application of micafungin, plasma samples were collected. Non-linear mixed effects modelling (NONMEM 7.3) was used to develop the pharmacokinetic model. Using this model, the adequacy of a fixed 100 mg dosing regimen was evaluated in the study cohort. A two-compartment model with linear elimination was found to describe the obtained data. SOFA score was identified as a significant covariate on both clearance and central volume of distribution, respectively. Patients in highly critical condition, represented by a SOFA above 10 showed a 30.8% lower central volume of distribution than the less critically ill patients. For patients with bilirubin levels above 4 mg/dl, clearance was decreased by 21.1%. Renal replacement therapy (RRT) did not influence micafungin clearance or the volumes of distribution. In a posthoc evaluation of the modeled population, 100 mg micafungin was suitable when assessing the PKPD targets (AUC/MIC) for C. albicans and C. glabrata, with insufficient target attainment for C. parapsilosis. Micafungin pharmacokinetics appear not to be influenced by the status of RRT. A dose of 100 mg micafungin is suitable for infections with C. albicans and C. glabrata in critically ill patients.
