Pharmacokinetics of Micafungin in Critically Ill Patients

Sci Rep. 2019 Nov 28;9(1):17741. doi: 10.1038/s41598-019-53093-6.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / pharmacokinetics*
  • Candida albicans / drug effects
  • Candida glabrata / drug effects
  • Candida parapsilosis / drug effects
  • Candidiasis / blood
  • Candidiasis / drug therapy
  • Critical Illness
  • Drug Monitoring
  • Female
  • Humans
  • Male
  • Micafungin / pharmacokinetics*
  • Middle Aged
  • Young Adult

Substances

  • Antifungal Agents
  • Micafungin