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  • Title: The effect of cimetidine on cyclosporine A levels in liver transplant recipients: a preliminary report.
    Author: Puff MR, Carey WD.
    Journal: Am J Gastroenterol; 1992 Mar; 87(3):287-91. PubMed ID: 1539561.
    Abstract:
    Both cimetidine and cyclosporine (CsA) are metabolized by the cytochrome P-450 system. Thus, coadministration of cimetidine and CsA may alter CsA metabolism. Because isoenzymes with the cytochrome P-450 system have variable drug-metabolizing effects, it is unclear whether a clinically significant drug-drug interaction will occur. We studied the acute effects of oral cimetidine administration on CsA metabolism in five orthotopic liver transplant patients and the chronic effects of oral cimetidine administration on CsA trough levels and liver and renal function in two. Cimetidine administration was associated with significantly higher CsA levels 60 and 120 min after an oral CsA dose (p = 0.004 and p = 0.002, respectively). Cimetidine had no effect on CsA levels drawn 240 and 480 min after the CsA dose or on trough levels. Cimetidine was found to have no effect on CsA trough levels when given over a 4-wk study period. Liver tests during the 4-wk period remained unchanged. Although there was a slight rise in serum creatinine, there was no change in blood urea nitrogen or renal clearance of [125I]iothalamate. We conclude that oral cimetidine administration significantly alters early CsA metabolism, but does not appreciably change CsA trough levels. Cimetidine appears safe to use in orthotopic liver transplant patients on CsA over at least a 4-wk period.
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