Optimization of Micafungin Dosage for Chinese Patients with Sepsis in the Intensive Care Unit Based on a Population Pharmacokinetic-Pharmacodynamic Analysis.

PURPOSE

This study aimed to identify parameters that influence micafungin pharmacokinetics in Chinese patients with sepsis in the intensive care unit and optimize micafungin dosage by determining the probability of reaching pharmacodynamic targets.

METHODS

Blood samples were collected from 32 Chinese patients with sepsis who were treated with micafungin. The samples were analyzed and used to build a population pharmacokinetic model. Monte Carlo simulations were performed to estimate the probability of achieving adequate plasma levels of micafungin against Candida species.

RESULTS

Alanine aminotransferase and sequential organ failure assessment score were found to significantly influence the clearance and peripheral distribution volume of micafungin, respectively. Monte Carlo simulations based on area under the plasma concentration-time curve over 24 h showed that patients must be administered at least 200 and 250 mg micafungin daily to reach minimum inhibitory concentration breakpoints of 0.032 and 0.064 mg/L for Candida glabrata and Candida tropicalis, respectively. Additionally, a probability of target attainment of ≥ 90% could not be achieved for Candida krusei or Candida parapsilosis with a 300 mg daily dose.

CONCLUSIONS

The recommended daily dose of micafungin (100 mg) may produce low clinical success ratios in non-Candida albicans infections; therefore, higher doses should be administered to improve clinical outcomes.