Micafungin population PK analysis in plasma and peritoneal fluid in septic patients with intra-abdominal infections: a prospective cohort study.

Abstract

Objectives: To describe the pharmacokinetics (PK) of micafungin in plasma and peritoneal fluid in septic patients with intra-abdominal infections.Methods: Twelve patients with secondary peritonitis in septic shock receiving 100 mg micafungin once daily were included. Total micafungin plasma and peritoneal fluid were subject to a population pharmacokinetic analysis using Pmetrics®. Monte Carlo simulations were performed considering total AUC0-24h/MIC ratios in plasma.Results: Micafungin concentrations in both plasma and peritoneal exudate were best described by a three-compartmental PK model with the fat free mass (FFM) as a covariate of clearance (CL) and volume of the central compartment (Vc). The mean parameter estimates (standard deviation, SD) were 1.18 (0.40) L/h for CL and 12.85 (4.78) L for Vc. The mean peritoneal exudate/plasma ratio (SD) of micafungin was 25% (5%) on day 1 and 40% (8%) between day 3-5. Dosing simulations supported the use of standard 100 mg daily dosing for C. albicans (FFM < 60 kg), C. glabrata (FFM < 50 kg) and C. tropicalis (FFM < 30 kg) on the second day of therapy.Conclusions: There is a moderate penetration of micafungin into peritoneal cavity (25 to 40%). For empirical treatment, a dose escalation of at least a loading dose of 150 mg depending on the FFM of patients and Candida species is suggested to be effective from the first day of therapy.