title: Pharmacokinetics of caspofungin in ICU patients.
abstract: OBJECTIVE
  Caspofungin is used for treatment of invasive fungal infections. As the pharmacokinetics (PK) of antimicrobial agents in critically ill patients can be highly variable, we set out to explore caspofungin PK in ICU patients.
  
  
  METHODS
  ICU patients receiving caspofungin were eligible. Patients received a loading dose of 70 mg followed by 50 mg daily (70 mg if body weight >80 kg); they were evaluable upon completion of the first PK curve at day 3. Additionally, daily trough samples were taken and a second PK curve was recorded at day 7. PK analysis was performed using a standard two-stage approach.
  
  
  RESULTS
  Twenty-one patients were evaluable. Median (range) age and body weight were 71 (45-80) years and 75 (50-99) kg. PK sampling on day 3 (n = 21) resulted in the following median (IQR) parameters: AUC0-24 88.7 (72.2-97.5) mg·h/L; Cmin 2.15 (1.40-2.48) mg/L; Cmax 7.51 (6.05-8.17) mg/L; V 7.72 (6.12-9.01) L; and CL 0.57 (0.54-0.77) L/h. PK sampling on day 7 (n = 13) resulted in AUC0-24 107.2 (90.4-125.3) mg·h/L, Cmin 2.55 (1.82-3.08) mg/L, Cmax 8.65 (7.16-9.34) mg/L, V 7.03 (5.51-7.73) L and CL 0.54 (0.44-0.60) L/h. We did not identify any covariates significantly affecting caspofungin PK in ICU patients (e.g. body weight, albumin, liver function). Caspofungin was well tolerated and no unexpected side effects were observed.
  
  
  CONCLUSIONS
  Caspofungin PK in ICU patients showed limited intraindividual and moderate interindividual variability, and caspofungin was well tolerated. A standard two-stage approach did not reveal significant covariates. Our study showed similar caspofungin PK parameters in ICU patients compared with non-critically ill patients.
authors.affiliation: Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands eline.muilwijk@radboudumc.nl.
authors.forename: E W
authors.initials: EW
authors.lastname: Muilwijk
authors.affiliation: Department of Intensive Care, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Schouten
authors.affiliation: Department of Intensive Care, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: van Leeuwen
authors.affiliation: Department of Intensive Care, Gelderse Vallei Hospital, Ede, The Netherlands.
authors.forename: A R H
authors.initials: AR
authors.lastname: van Zanten
authors.affiliation: Department of Intensive Care and National Poison Information Center, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: D W
authors.initials: DW
authors.lastname: de Lange
authors.affiliation: Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Colbers
authors.affiliation: Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: P E
authors.initials: PE
authors.lastname: Verweij
authors.affiliation: Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: D M
authors.initials: DM
authors.lastname: Burger
authors.affiliation: Department of Intensive Care, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Pickkers
authors.affiliation: Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: R J M
authors.initials: RJ
authors.lastname: Brüggemann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077336:Caspofungin; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness; D054714:Echinocandins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin
keywords: PK; antifungal drugs; echinocandins; intensive care units