Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers

Clin Pharmacol Ther. 2010 Jun;87(6):663-7. doi: 10.1038/clpt.2009.266. Epub 2010 Mar 10.

Abstract

Organ transplant recipients who have dyslipidemia related to immunosuppression may benefit from cholesterol-lowering therapy with ezetimibe, a substrate of ABCB1, ABCC2, and OATP1B1. Adverse pharmacokinetic interactions are hypothesized with sirolimus, which is a substrate of OATP1B1 and OATP1B3 and an inhibitor of ABCB1, OATP1B1, and OATP1B3 but not of ABCC2. However, competition between sirolimus and ezetimibe for ABCB1 and OATP1B1 is not of major clinical relevance, as confirmed in our randomized, controlled, single-dose study in healthy subjects.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / pharmacokinetics*
  • Anticholesteremic Agents / pharmacology
  • Azetidines / administration & dosage
  • Azetidines / pharmacokinetics*
  • Azetidines / pharmacology
  • Cell Line
  • Cells, Cultured
  • Cross-Over Studies
  • Dogs
  • Dose-Response Relationship, Drug
  • Ezetimibe
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / pharmacology
  • Male
  • Organic Anion Transporters / metabolism
  • Sirolimus / administration & dosage
  • Sirolimus / pharmacokinetics*
  • Sirolimus / pharmacology
  • Transfection
  • Young Adult

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Immunosuppressive Agents
  • Organic Anion Transporters
  • Ezetimibe
  • Sirolimus