title: Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Grau
authors.affiliation: Pharmacy Department, Hospital del Mar, Barcelona, Spain Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Luque
authors.affiliation: Pharmacy Department, Hospital del Mar, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Campillo
authors.affiliation: Anaesthesiology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Samsó
authors.affiliation: Anaesthesiology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: U
authors.initials: U
authors.lastname: Rodríguez
authors.affiliation: Anaesthesiology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: C A
authors.initials: CA
authors.lastname: García-Bernedo
authors.affiliation: Pharmacy Department, Hospital del Mar, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Salas
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: W W
authors.initials: WW
authors.lastname: Hope
authors.affiliation: 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.
authors.forename: J A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001202:Ascitic Fluid; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D016638:Critical Illness; D016903:Drug Monitoring; D054714:Echinocandins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D055666:Lipopeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D010538:Peritonitis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D010949:Plasma; D011183:Postoperative Complications; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin