Single- and multiple-dose administration of caspofungin in patients with hepatic insufficiency: implications for safety and dosing recommendations

J Clin Pharmacol. 2007 Aug;47(8):951-61. doi: 10.1177/0091270007303764.

Abstract

This report investigated safety and dosing recommendations of intravenous caspofungin in hepatic insufficiency. In the single-dose study, 8 patients each with mild and moderate hepatic insufficiency received 70 mg of caspofungin. In the multiple-dose study, 8 patients with mild hepatic insufficiency and 13 healthy matched controls received 70 mg on day 1 and 50 mg daily on days 2 through 14. Eight patients with moderate hepatic insufficiency received 70 mg on day 1 and 35 mg daily on days 2 through 14. Caspofungin was generally well tolerated with no discontinuations due to serious or nonserious adverse experiences. The area under the concentration-time profile over the interval of last quantifiable point to infinity (AUC(0-infinity)) geometric mean ratio (GMR) (90% confidence interval [CI]) for mild hepatic insufficiency/historical controls was 1.55 (1.32-1.86) in the single-dose study and for mild hepatic insufficiency/concurrent controls was 1.21 (1.04-1.39) for day 14 area under the concentration-time profile calculated over the interval 0 to 24 hours (AUC(0-24h)) following multidose. The AUC(0-infinity) GMR (90% CI) for moderate hepatic insufficiency/historical controls was 1.76 (1.51-2.06) following 70 mg; AUC(0-24h) GMR (90% CI) for moderate hepatic insufficiency/concurrent controls was 1.07 (0.90-1.28) on day 14 after 35 mg daily. No dosage adjustment is recommended for patients with mild hepatic insufficiency. A dosage reduction to 35 mg daily following the 70-mg loading dose is recommended for patients with moderate hepatic insufficiency.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / adverse effects*
  • Antifungal Agents / pharmacokinetics
  • Area Under Curve
  • Caspofungin
  • Echinocandins
  • Female
  • Hepatic Insufficiency / metabolism*
  • Humans
  • Injections, Intravenous
  • Lipopeptides
  • Male
  • Middle Aged
  • Peptides, Cyclic / administration & dosage*
  • Peptides, Cyclic / adverse effects*
  • Peptides, Cyclic / pharmacokinetics

Substances

  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Peptides, Cyclic
  • Caspofungin