Pharmacokinetics of cyclosporine in hyperlipidaemic long-term survivors of heart transplantation. Lack of interaction with the lipid-lowering agent, fenofibrate

Eur J Clin Pharmacol. 1992;43(2):161-5. doi: 10.1007/BF01740664.

Abstract

Cyclosporine (Cy) binds to lipoproteins in plasma. In order to test if its pharmacokinetics would be modified when efficient lipid-lowering treatment is introduced, a study has been done of Cy pharmacokinetics and any interaction with the lipid-lowering agent fenofibrate in hyperlipidaemic long-term, survivors of heart transplantation. Fenofibrate 200 mg once daily significantly reduced blood lipids (cholesterol 6.5 vs 7.7 mmol/l; apoprotein B 1.2 vs 1.6 g/l) but did not modify mean whole blood Cy trough levels (113 before fenofibrate vs 103 ng.ml-1), Cmax (812 ng.ml-1 by RIA and 757 ng.ml-1 by HPLC before fenofibrate versus 865 and 741 respectively, during fenofibrate); tmax (1.6 and 1.7 h before fenofibrate versus 1.4 and 1.4 h respectively), and t1/2 (13.9 and 11.1 h versus 9.5 and 10.7 h). The only adverse effect was an increase in creatinine (157 vs 145 mmol/l). Further studies are needed to investigate the mechanism of Cy-fenofibrate nephrotoxicity and to evaluate the long-term efficiency and safety of fenofibrate after heart transplantation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chromatography, High Pressure Liquid
  • Cyclosporine / blood
  • Cyclosporine / pharmacokinetics*
  • Fenofibrate / pharmacology*
  • Heart Transplantation* / mortality
  • Humans
  • Hyperlipidemias / metabolism*
  • Male
  • Middle Aged
  • Radioimmunoassay
  • Time Factors

Substances

  • Cyclosporine
  • Fenofibrate