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  • Title: Cyclosporine-cimetidine interaction.
    Author: D'Souza MJ, Pollock SH, Solomon HM.
    Journal: Drug Metab Dispos; 1988; 16(1):57-9. PubMed ID: 2894956.
    Abstract:
    Cyclosporine (CsA) is used to prevent rejection of transplanted organs. It is extensively metabolized in the liver by the mixed function oxidase enzyme system by demethylation and hydroxylation. Since cimetidine is a widely prescribed H2 antagonist drug which is known to inhibit the P-450 enzyme system, we studied the effect of chronic treatment with cimetidine on CsA by determining the disposition of CsA (15 mg/kg, iv), prior to and after chronic treatment with cimetidine (60 mg/kg, po), for 5 days. CsA was determined by an HPLC procedure. The clearance (Cl) of CsA was significantly reduced following treatment with cimetidine when compared to the Cl value obtained in the control group (15.46 versus 10.36 ml/min/kg). There were no significant changes in the volume of distribution of CsA, one reason being that cimetidine and cyclosporine bind to different proteins. From the results obtained, we conclude that since cimetidine is an inhibitor of the mixed function oxidase system enzyme system, it inhibits the metabolism of CsA.
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