Involvement of multidrug resistance-associated protein 2 (ABCC2/Mrp2) in biliary excretion of micafungin in rats

Life Sci. 2008 Aug 15;83(7-8):229-35. doi: 10.1016/j.lfs.2008.06.013. Epub 2008 Jul 1.

Abstract

The drug transporter, multidrug resistance-associated protein 2 (ABCC2/Mrp2), is known to play important roles in excretion of various drugs. In the present study, we investigated whether Mrp2 is involved in the transport of micafungin, a newly developed antifungal agent. When Sprague-Dawley rats received an intravenous injection of micafungin (1 mg/kg) in combination with cyclosporine, the cyclosporine significantly delayed the disappearance of micafungin from plasma and decreased the systemic clearance and volume of distribution at steady-state of micafungin to 54% and 65% of the corresponding control values, respectively. When Sprague-Dawley rats received a constant-rate infusion of micafungin, cyclosporine significantly decreased the steady-state biliary clearance of micafungin (approximately 80%). A significant decrease in the biliary clearance of micafungin (~60%) was observed in Eisai hyperbilirubinemic rats, which have a hereditary deficiency in Mrp2. The present findings at least suggest that Mrp2 is involved mainly in the hepatobiliary excretion of micafungin in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Antifungal Agents / pharmacokinetics*
  • Bile / metabolism*
  • Biological Transport / drug effects
  • Biological Transport / genetics
  • Cyclosporine / pharmacology
  • Echinocandins / pharmacokinetics*
  • Enzyme Inhibitors / pharmacology
  • Hyperbilirubinemia
  • Injections, Intravenous
  • Lipopeptides
  • Lipoproteins / pharmacokinetics*
  • Male
  • Micafungin
  • Rats
  • Rats, Sprague-Dawley

Substances

  • ATP-Binding Cassette Transporters
  • Abcc2 protein, rat
  • Antifungal Agents
  • Echinocandins
  • Enzyme Inhibitors
  • Lipopeptides
  • Lipoproteins
  • Cyclosporine
  • Micafungin