Interaction of single-dose ezetimibe and steady-state cyclosporine in renal transplant patients

J Clin Pharmacol. 2006 Mar;46(3):328-36. doi: 10.1177/0091270005284852.

Abstract

This open-label, single-period study evaluated the single-dose pharmacokinetics of ezetimibe (EZE) 10 mg in the setting of steady-state cyclosporine (CyA) dosing in renal transplant patients. A single 10-mg dose of EZE was coadministered with the morning dose of CyA (75-150 mg twice a day). Total EZE (sum of unconjugated, parent EZE and EZE-glucuronide; EZE-total) AUC(0-last) and Cmax were compared to values derived from a prespecified database of healthy volunteers. Geometric mean ratios (90% CIs) for (EZE + CyA)/EZE alone for EZE-total AUC((0-last)) and Cmax were 3.41 (2.55, 4.56) and 3.91 (3.13, 4.89), respectively. Compared to healthy controls, EZE-total AUC((0-last)) was 3.4-fold higher in transplant patients receiving CyA; similar exposure levels were seen in a prior multiple-dose study in which EZE 50 mg was administered to healthy volunteers without dose-related toxicity. Because the long-term safety implications of both higher EZE exposures and undetermined effect on CyA are not yet understood, the clinical significance of this interaction is unknown.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticholesteremic Agents / blood
  • Anticholesteremic Agents / pharmacokinetics*
  • Area Under Curve
  • Azetidines / blood
  • Azetidines / pharmacokinetics*
  • Cyclosporine / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Monitoring
  • Ezetimibe
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Kidney Transplantation*
  • Male
  • Middle Aged

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Immunosuppressive Agents
  • Cyclosporine
  • Ezetimibe