Prospective Cohort Study of Micafungin Population Pharmacokinetic Analysis in Plasma and Peritoneal Fluid in Septic Patients with Intra-abdominal Infections - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Antimicrobial Agents and Chemotherapy Année : 2021

Prospective Cohort Study of Micafungin Population Pharmacokinetic Analysis in Plasma and Peritoneal Fluid in Septic Patients with Intra-abdominal Infections

Résumé

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.

Dates et versions

hal-03633057 , version 1 (06-04-2022)

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Citer

Nicolas Garbez, Litaty Mbatchi, Steven Wallis, Laurent Muller, Jeffrey Lipman, et al.. Prospective Cohort Study of Micafungin Population Pharmacokinetic Analysis in Plasma and Peritoneal Fluid in Septic Patients with Intra-abdominal Infections. Antimicrobial Agents and Chemotherapy, 2021, 65 (7), pp.e0230720. ⟨10.1128/AAC.02307-20⟩. ⟨hal-03633057⟩
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