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Pharmacokinetic interaction between oral cyclosporin and mibefradil in stabilized post-renal-transplant patients

Spoendlin, M. ; Peters, J. ; Welker, H. ; Bock, A. ; Thiel, G.

In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 1998, vol. 13, no. 7, p. 1787-1791

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    Titel
    • Pharmacokinetic interaction between oral cyclosporin and mibefradil in stabilized post-renal-transplant patients
    Autor
    • Spoendlin, M.. Division of Nephrology, University of Basel, Kantonsspital, Switzerland.
    • Peters, J.. Division of Nephrology, University of Basel, Kantonsspital, Switzerland.
    • Welker, H.. Division of Nephrology, University of Basel, Kantonsspital, Switzerland.
    • Bock, A.. Division of Nephrology, University of Basel, Kantonsspital, Switzerland.
    • Thiel, G.. Division of Nephrology, University of Basel, Kantonsspital, Switzerland.
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 1998, vol. 13, no. 7, p. 1787-1791
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:294881
    Summary
    BACKGROUND: The potential for interaction between oral cyclosporin (Sandimmun) and the new calcium antagonist mibefradil was assessed as part of the clinical development of the new compound. METHODS: Six stable renal transplant patients on long-term, oral, twice-daily (Q 12 H) cyclosporin (CsA) therapy received 25 mg mibefradil on Day 1, followed by 50 mg once daily for 5 or 6 days. At baseline, as well as on the last day of mibefradil dosing, complete steady-state CsA blood concentration-time profiles were characterized over a dosing interval. RESULTS: Mibefradil led to mean increases in minimum and maximum CsA blood concentrations and area under the curve of CsA by 2.7-, 2.1-, and 2.3-fold, respectively (all significantly different from CsA alone, P < 0.02). Mibefradil is therefore associated with a clinically relevant increase in CsA blood concentrations. The mechanism of elevation of CsA blood concentrations is probably mibefradil and/or metabolite inhibition of the cytochrome P-450 isoenzyme 3A4. CsA had no clinically significant effect on mibefradil plasma concentrations. CONCLUSIONS: These results confirm previous findings of cytochrome P-450 3A4 inhibition by mibefradil and suggest that, for patients receiving CsA, its dose must be adjusted and its plasma concentration must be monitored when adding or stopping mibefradil