Cyclosporin Metabolism in Human Liver Microsomes and Its Inhibition by Other Drugs

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Abstract
The metabolism of cyclosporin was studied in human liver microsomes. There was no metabolism in the presence of cytochrome C or carbon monoxide or in the absence of cofactors, suggesting metabolism by cytochrome P‐450 enzymes. The metabolism was inhibited by ketoconazole and erythromycin, by the steroids methylprednisolone and oestradiol, and by the calcium antagonists diltiazem, nifedipine, prenylamine and verapamil. Thesein vitrofindings correlate well with previously published clinical reports suggesting that these drugs may inhibit the metabolism of cyclosporinin vivo.Our observations suggest that metabolic interactions between cyclosporin and other drugsin vivomay be predictedin vitrounder proper experimental conditions.