EFFECTS OF FLUCONAZOLE ON PHARMACOKINETICS OF TACROLIMUS

$0M01FY2000RRNIH

University Of California San Francisco, San Francisco CA

Investigators

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Abstract

Tacrolimus (TAC) is a potent immunosuppressant used primarily for the prevention of allograft rejection in liver transplant. TAC is poorly and erratically absorbed after oral administration with its bioavailability averaging 25-30%. Interaction of TAC with p-glycoprotein and CYP3A may be the cause of the low and highly variable bioavailability of this agent. Studies from our lab and others have demonstrated that intestinal metabolism is an important determinant of tacrolimus bioavailability. This study is designed to demonstrate that intestinal p-glycoprotein plays a major role in the absorption and bioavailability of TAC. It will allow us to evaluate the extent to which administration of fluconazole, given orally or intravenously, affects the pharmacokinetics of TAC, with particular emphasis on possible differences in the effects of fluconazole on p-glycoprotein in both liver and gut. The GCRC facility will allow us to study our human subjects in an outpatient setting.

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