PMID: 9000641Jan 1, 1997Paper

Decrease in oral bioavailability of cyclosporin A by coadministration of probucol in rats

Life Sciences
K SugimotoA Fujimura

Abstract

To assess the pharmacokinetic interaction of cyclosporin A with probucol, we administered cyclosporin A (10 mg/kg body weight) to rats orally or intravenously with or without pretreatment of probucol (10 mg/animal, daily for 8 days). The whole blood cyclosporin A concentration-time curves after oral administration showed a 34% reduction in peak concentration and a 30% decrease in area under the blood concentration-time curve (AUC) by administration of probucol. No apparent change in elimination half-life or volume of the central compartment was observed with the treatment of probucol. After intravenous administration of cyclosporin A, the blood levels could be described by a two-compartment open model. No differences were observed in the AUC, elimination half-life or total clearance of cyclosporin A by the pretreatment of probucol. Calculated bioavailability following oral administration of cyclosporin A decreased by 33% with the treatment of probucol. These results suggest that probucol may not profoundly influence the disposition of cyclosporin A. Coadministration of probucol could decrease the fraction of absorbed cyclosporin A after oral administration.

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Citations

Jul 7, 2005·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Melanie L BlackhallJeff S Coombes
Apr 29, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Koh-ichi SugimotoAkio Fujimura

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