Concomitant cyclosporine and micafungin pharmacokinetics in healthy volunteers

J Clin Pharmacol. 2005 Aug;45(8):954-60. doi: 10.1177/0091270005278601.

Abstract

Cyclosporine is a marketed immunosuppressive agent and a known substrate for CYP3A. Micafungin is an antifungal agent and a mild inhibitor of CYP3A-mediated metabolism in vitro. The objectives of this study were to evaluate the pharmacokinetics of cyclosporine and micafungin before and with concomitant administration. The pharmacokinetics of single-dose oral cyclosporine (5 mg/kg) were estimated on days 1, 9, and 15 (n = 27). Subjects received micafungin (100 mg/d over 1 hour) on days 7, 9, and 11 through 15. Micafungin pharmacokinetics were estimated on days 7, 9, and 15. Mean apparent oral cyclosporine clearances were estimated to be 645+/-236 mL/h/kg, 546+/-101 mL/h/kg (P = .01), and 540+/-104 mL/h/kg (P = .02) for days 1, 9, and 15, respectively. Micafungin appears to be a mild inhibitor of cyclosporine metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / pharmacology*
  • Area Under Curve
  • Cyclosporine / administration & dosage
  • Cyclosporine / blood
  • Cyclosporine / pharmacokinetics*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Echinocandins
  • Female
  • Half-Life
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics*
  • Lipopeptides
  • Lipoproteins / administration & dosage
  • Lipoproteins / pharmacology*
  • Male
  • Metabolic Clearance Rate
  • Micafungin
  • Middle Aged
  • Peptides, Cyclic / administration & dosage
  • Peptides, Cyclic / pharmacology*

Substances

  • Antifungal Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Echinocandins
  • Immunosuppressive Agents
  • Lipopeptides
  • Lipoproteins
  • Peptides, Cyclic
  • Cyclosporine
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Micafungin