Pharmacokinetic study of anidulafungin in ICU patients with intra-abdominal candidiasis

J Antimicrob Chemother. 2017 May 1;72(5):1429-1432. doi: 10.1093/jac/dkw568.

Abstract

Background: Only limited pharmacokinetic data are available for anidulafungin in ICU patients, especially in patients treated for severe intra-abdominal infection (IAI).

Methods: This was a prospective multicentre observational study in ICU patients with suspected yeast IAI. All patients received an intravenous loading dose of 200 mg of anidulafungin, followed by 100 mg/day. Thirteen blood samples were drawn between day 1 and day 5 for pharmacokinetic analysis. Samples were analysed by an HPLC-tandem MS method. Demographics and SAPS2 and SOFA scores were recorded.

Results: Fourteen patients with a median age (IQR) of 62 years (48-70) and with a mean BMI of 30.5 kg/m 2 were included from three centres; 57.1% were women. Their median (IQR) SAPS2 score was 54 (45-67) and their median (IQR) SOFA score was 8 (7-12). Six patients with community-acquired IAI and eight patients with nosocomial-acquired IAI were included. Twelve yeasts were isolated: six Candida albicans , two Candida glabrata , two Candida tropicalis , one Candida parapsilosis and one Candida krusei . Pharmacokinetic parameters were as follows [mean (% coefficient of variation)]: C max (mg/L) = 6.0 (29%); T max (h) = 1.6 (25.8%); C min (mg/L) = 3.2 (36.8%); AUC 0-24 (mg·h/L) = 88.9 (38.6%); t 1/2 (h) = 42.1 (68.2%); CL (L/h) = 1.2 (42.3%); and V (L) = 72.8 (87.8%). A two-compartment model best described the anidulafungin concentrations in the population pharmacokinetic study.

Conclusions: The pharmacokinetic parameters of anidulafungin in critically ill ICU patients with complicated IAI are similar to those observed in the literature. However, an increased V and a longer t 1/2 were observed in this study. (EudraCT No. 2010-018695-25).

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Administration, Intravenous
  • Aged
  • Anidulafungin
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics*
  • Antifungal Agents / therapeutic use
  • Candida / drug effects*
  • Candida / isolation & purification
  • Candida albicans / drug effects
  • Candida albicans / isolation & purification
  • Candida glabrata / drug effects
  • Candida glabrata / isolation & purification
  • Candida tropicalis / drug effects
  • Candida tropicalis / isolation & purification
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Chromatography, High Pressure Liquid
  • Critical Illness
  • Echinocandins / administration & dosage
  • Echinocandins / blood
  • Echinocandins / pharmacokinetics*
  • Echinocandins / therapeutic use
  • Female
  • Humans
  • Intensive Care Units*
  • Intraabdominal Infections / drug therapy*
  • Intraabdominal Infections / microbiology
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Prospective Studies

Substances

  • Antifungal Agents
  • Echinocandins
  • Anidulafungin