Pharmacokinetics of anidulafungin in critically ill patients with candidemia/invasive candidiasis

Antimicrob Agents Chemother. 2013 Apr;57(4):1672-6. doi: 10.1128/AAC.02139-12. Epub 2013 Jan 18.

Abstract

The pharmacokinetics of intravenous anidulafungin in adult intensive care unit (ICU) patients were assessed in this study and compared with historical data from a general patient population and healthy subjects. Intensive plasma sampling was performed over a dosing interval at steady state from 21 ICU patients with candidemia/invasive candidiasis. All patients received the recommended dosing regimen (a 200-mg loading dose on day 1, followed by a daily 100-mg maintenance dose), except for a 54-year-old 240-kg female patient (who received a daily 150-mg maintenance dose instead). Plasma samples were assayed for anidulafungin using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters in ICU patients were calculated by a noncompartmental method. With the exclusion of the 240-kg patient, the median (minimum, maximum) age, weight, and body mass index (BMI) of 20 ICU patients were 57 (39, 78) years, 65 (48, 106) kg, and 23.3 (16.2, 33.8) kg/m(2), respectively. The average anidulafungin area under the curve over the 24-hour dosing interval (AUC(0-24)), maximum concentration (C(max)), and clearance (CL) in 20 ICU patients were 92.7 mg · h/liter, 7.7 mg/liter, and 1.3 liters/h, respectively. The exposure in the 240-kg patient at a daily 150-mg dose was within the range observed in ICU patients overall. The average AUC(0-24) and Cmax in the general patient population and healthy subjects were 110.3 and 105.9 mg · h/liter and 7.2 and 7.0 mg/liter, respectively. The pharmacokinetics of anidulafungin in ICU patients appeared to be comparable to those in the general patient population and healthy subjects at the same dosing regimen.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anidulafungin
  • Antifungal Agents / pharmacokinetics*
  • Antifungal Agents / therapeutic use*
  • Candidemia / blood
  • Candidemia / drug therapy*
  • Candidiasis, Invasive / blood
  • Candidiasis, Invasive / drug therapy*
  • Critical Illness*
  • Echinocandins / pharmacokinetics*
  • Echinocandins / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged

Substances

  • Antifungal Agents
  • Echinocandins
  • Anidulafungin