Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis

Objectives

Limited information about the pharmacokinetics of micafungin in the peritoneal cavity is available. The aim of this study was to explore the pharmacokinetics/pharmacodynamics of micafungin in plasma and peritoneal fluid in post-surgical critically ill patients with proven or suspected intra-abdominal fungal infection.

Methods

Patients were administered 100 mg/day micafungin. Serial blood and peritoneal fluid samples were collected on day 1 and day 3 (steady-state) of treatment. Concentrations were determined by validated chromatography and were subject to a population pharmacokinetic analysis with Pmetrics®. Monte Carlo simulations were performed for AUC0–24/MIC ratios in plasma. The PTA was calculated using AUC0–24/MIC cut-offs: 285 for Candida parapsilosis and 3000 for non-parapsilosis Candida spp.

Results

Ten patients were included; six were male. The median (range) age, APACHE II score and Mannheim peritonitis index were 72 (43–85) years, 15 (11–36) and 26 (8–37), respectively. On day 1, median (SD) penetration of micafungin into the peritoneal cavity was 30% (30%–40%). A three-compartment model adequately described the data. The mean (SD) estimates for clearance and volume of distribution of the central compartment were 1.27 (0.75) L/h and 9.26 (1.11) L, respectively. In most patients, the PTA in plasma was ≥90% for MICs of 0.008–0.016 mg/L for Candida spp. and 0.125–0.25 mg/L for C. parapsilosis.

Conclusions

After the first dose, micafungin at 100 mg/day achieves pharmacokinetic/pharmacodynamic targets in plasma for Candida spp. and C. parapsilosis MICs of 0.008–0.016 and 0.125–0.25 mg/L, respectively.