Dose Reduction of Caspofungin in Intensive Care Unit Patients with Child Pugh B Will Result in Suboptimal Exposure

Clin Pharmacokinet. 2016 Jun;55(6):723-33. doi: 10.1007/s40262-015-0347-2.


Background and objectives: Caspofungin is an echinocandin antifungal agent used as first-line therapy for the treatment of invasive candidiasis. The maintenance dose is adapted to body weight (BW) or liver function (Child-Pugh score B or C). We aimed to study the pharmacokinetics of caspofungin and assess pharmacokinetic target attainment for various dosing strategies.

Methods: Caspofungin pharmacokinetic data from 21 intensive care unit (ICU) patients was available. A population pharmacokinetic model was developed. Various dosing regimens (loading dose/maintenance dose) were simulated: licensed regimens (I) 70/50 mg (for BW <80 kg) or 70/70 mg (for BW >80 kg); and (II) 70/35 mg (for Child-Pugh score B); and adapted regimens (III) 100/50 mg (for Child-Pugh score B); (IV) 100/70 mg; and (V) 100/100 mg. Target attainment based on a preclinical pharmacokinetic target for Candida albicans was assessed for relevant minimal inhibitory concentrations (MICs).

Results: A two-compartment model best fitted the data. Clearance was 0.55 L/h and the apparent volumes of distribution in the central and peripheral compartments were 8.9 and 5.0 L, respectively. The median area under the plasma concentration-time curve from time zero to 24 h on day 14 for regimens I-V were 105, 65, 93, 130, and 186 mg·h/L, respectively. Pharmacokinetic target attainment was 100 % (MIC 0.03 µg/mL) irrespective of dosing regimen but decreased to (I) 47 %, (II) 14 %, (III) 36 %, (IV) 69 %, and (V) 94 % for MIC 0.125 µg/mL.

Conclusion: The caspofungin maintenance dose should not be reduced in non-cirrhotic ICU patients based on the Child-Pugh score if this classification is driven by hypoalbuminemia as it results in significantly lower exposure. A higher maintenance dose of 70 mg in ICU patients results in target attainment of >90 % of the ICU patients with species with an MIC of up to 0.125 µg/mL.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / therapeutic use
  • Body Mass Index
  • Candidiasis / drug therapy*
  • Caspofungin
  • Dose-Response Relationship, Drug
  • Echinocandins / administration & dosage*
  • Echinocandins / therapeutic use
  • Female
  • Humans
  • Intensive Care Units*
  • Lipopeptides / administration & dosage*
  • Lipopeptides / therapeutic use
  • Male
  • Metabolic Clearance Rate
  • Microbial Sensitivity Tests
  • Middle Aged
  • Models, Biological
  • Monte Carlo Method
  • Severity of Illness Index
  • Young Adult


  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Caspofungin

Supplementary concepts

  • Systemic candidiasis