Format

Send to

Choose Destination
J Antimicrob Chemother. 2015 Oct;70(10):2854-61. doi: 10.1093/jac/dkv173. Epub 2015 Jul 14.

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

Author information

1
Pharmacy Department, Hospital del Mar, Barcelona, Spain Universitat Autónoma de Barcelona, Barcelona, Spain Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain sgrau@parcsalutmar.cat.
2
Pharmacy Department, Hospital del Mar, Barcelona, Spain Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
3
Pharmacy Department, Hospital del Mar, Barcelona, Spain.
4
Anaesthesiology Department, Hospital del Mar, Barcelona, Spain.
5
Liverpool School of Tropical Medicine, Liverpool, UK.
6
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
7
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Australia.

Abstract

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.

PMID:
26180134
DOI:
10.1093/jac/dkv173
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center