Prospective Cohort Study of Micafungin Population Pharmacokinetic Analysis in Plasma and Peritoneal Fluid in Septic Patients with Intra-abdominal Infections.
The objective of this study was to describe the pharmacokinetics (PK) of micafungin in plasma and peritoneal fluid in septic patients with intra-abdominal infections. Twelve patients with secondary peritonitis in septic shock receiving 100 mg micafungin once daily were included. Total micafungin plasma and peritoneal fluid were subjected to a population pharmacokinetic analysis using Pmetrics. Monte Carlo simulations were performed considering the total area under the curve from 0 to 24 h (AUC0-24)/MIC ratios in plasma. Micafungin concentrations in both plasma and the peritoneal exudate were best described by a three-compartmental PK model with the fat-free mass (FFM) as a covariate of clearance (CL) and the volume of the central compartment (Vc). The mean parameter estimates (standard deviations [SD]) were 1.18 (0.40) liters/h for CL and 12.85 (4.78) liters for Vc. The mean peritoneal exudate/plasma ratios (SD) of micafungin were 25% (5%) on day 1 and 40% (8%) between days 3 and 5. Dosing simulations supported the use of standard 100-mg daily dosing for Candida albicans (FFM, <60 kg), C. glabrata (FFM, <50 kg), and C. tropicalis (FFM, <30 kg) on the second day of therapy. There is a moderate penetration of micafungin into the 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 the Candida species is suggested to be effective from the first day of therapy.
['Garbez|Nicolas|N|', 'Mbatchi|Litaty|L|', 'Wallis|Steven C|SC|', 'Muller|Laurent|L|', 'Lipman|Jeffrey|J|', 'Roberts|Jason A|JA|', 'Lefrant|Jean-Yves|JY|', 'Roger|Claire|C|']
D000935:Antifungal Agents D001202:Ascitic Fluid D054714:Echinocandins D006801:Humans D059413:Intraabdominal Infections D055666:Lipopeptides D000077551:Micafungin D008826:Microbial Sensitivity Tests D009010:Monte Carlo Method D011446:Prospective Studies D018805:Sepsis
micafungin pharmacokinetics peritoneal fluid secondary peritonitis septic shock Monte Carlo simulations intensive care unit