Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis.
J Antimicrob Chemother
; 70(10): 2854-61, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26180134
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peritonite
/
Complicações Pós-Operatórias
/
Equinocandinas
/
Lipopeptídeos
/
Antifúngicos
Tipo de estudo:
Diagnostic_studies
/
Health_economic_evaluation
/
Observational_studies
/
Prognostic_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Espanha