title: Pharmacokinetics of Anidulafungin in Critically Ill Intensive Care Unit Patients with Suspected or Proven Invasive Fungal Infections.
abstract: Echinocandins, such as anidulafungin, are the first-line treatment for candidemia or invasive candidiasis in critically ill patients. There are conflicting data on the pharmacokinetic properties of anidulafungin in intensive care unit (ICU) patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included in the present study. Patients were considered evaluable if a pharmacokinetic curve for day 3 could be completed. Twenty-three of 36 patients (7 female and 16 male) were evaluable. The median (range) age and body weight were 66 (28 to 88) years and 76 (50 to 115) kg, respectively. Pharmacokinetic sampling on day 3 (n = 23) resulted in a median anidulafungin area under the concentration-time curve from 0 to 24 h (AUC0-24) of 72.1 (interquartile range [IQR], 61.3 to 94.0) mg · h · liter-1, a median daily trough concentration (C24) of 2.2 (IQR, 1.9 to 2.9) mg/liter, a median maximum concentration of drug in serum (Cmax) of 5.3 (IQR, 4.1 to 6.0) mg/liter, a median volume of distribution (V) of 46.0 (IQR, 32.2 to 60.2) liters, and a median clearance (CL) of 1.4 (IQR, 1.1 to 1.6) liters · h-1Pharmacokinetic sampling on day 7 (n = 13) resulted in a median AUC0-24of 82.7 (IQR, 73.0 to 129.5) mg · h · liter-1, a median minimum concentration of drug in serum (Cmin) of 2.8 (IQR, 2.2 to 4.2) mg/liter, a median Cmaxof 5.9 (IQR, 4.6 to 8.0) mg/liter, a median V of 39.7 (IQR, 32.2 to 54.4) liters, and a median CL of 1.2 (IQR, 0.8 to 1.4) liters · h-1The geometric mean ratio for the AUCday7/AUCday3term was 1.13 (90% confidence interval [CI], 1.03 to 1.25). The exposure in the ICU patient population was in accordance with previous reports on anidulafungin pharmacokinetics in ICU patients but was lower than that for healthy volunteers or other patient populations. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates. (This study has been registered at ClinicalTrials.gov under identifier NCT01438216.).
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, and Center of Expertise in Mycology, Radboudumc/CWZ, Nijmegen, The Netherlands roger.bruggemann@radboudumc.nl.
authors.forename: R J M
authors.initials: RJ
authors.lastname: Brüggemann
authors.affiliation: Department of Pharmacy, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Middel-Baars
authors.affiliation: Department of Intensive Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: D W
authors.initials: DW
authors.lastname: de Lange
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, and Center of Expertise in Mycology, Radboudumc/CWZ, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Colbers
authors.affiliation: Department of Intensive Care, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: A R J
authors.initials: AR
authors.lastname: Girbes
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, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: E L
authors.initials: EL
authors.lastname: Swart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016638:Critical Illness; D054714:Echinocandins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D000072742:Invasive Fungal Infections / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D000077612:Anidulafungin
keywords: antifungal drugs; echinocandins; intensive care unit; invasive fungal infections; pharmacokinetics