Influence of Co-medication with sirolimus or cyclosporine on mycophenolic acid pharmacokinetics in kidney transplantation

D. Cattaneo, S. Merlini, S. Zenoni, S. Baldelli, E. Gotti, G. Remuzzi, N. Perico

Research output: Contribution to journalArticlepeer-review

Abstract

The pharmacokinetics of mycophenolic acid (MPA) - the active metabolite of mycophenolate mofetil (MMF) - is significantly influenced by co-medications. The impact of sirolimus on daily MPA exposure, however, has not been investigated so far. As a part of the study aimed at investigating the efficacy of Campath-1H induction therapy in a steroid-free regimen in kidney transplantation, MPA plasma levels were serially measured in 21 patients treated with low-dose sirolimus (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post-operatively. Full pharmacokinetic profiles were compared at month 6 and 12 post-surgery. Mean dose-adjusted MPA trough levels were 4.4-fold higher in patients on combined SRL and MMF than in those given CsA and MMF. Pharmacokinetic studies demonstrated that mean MPA Cmax and T max were comparable in the two groups, while mean MPA AUC 0-12 was higher in SRL than CsA treated patients. The pharmacokinetic profile of SRL- but not of CsA-group showed a second peak consistent with the enterohepatic recirculation of MPA. These findings suggest that SRL and CsA have different effects on MPA metabolism and/or excretion eventually affecting its immunosuppressive property and/or toxicity. CsA, but not SRL, inhibits MPA enterohepatic recirculation, reducing MPA daily exposure.

Original languageEnglish
Pages (from-to)2937-2944
Number of pages8
JournalAmerican Journal of Transplantation
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 2005

Keywords

  • Cyclosporine
  • Drug-drug interactions
  • Kidney transplantation
  • Mycophenolic acid
  • Pharmacokinetics
  • Sirolimus

ASJC Scopus subject areas

  • Immunology

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