Drug Interactions Between Caspofungin and Tacrolimus

J. STONE1, S. HOLLAND1, P. WICKERSHAM1, P. DEUTSCH1, G. WINCHELL1, M. HESNEY1, R. MILLER1, A. FREEMAN1, S. DILZER2, K. LASSETER2

Author address: 

1Merck Research Laboratories, West Point, PA, 2Clinical Pharmacology Associates, Miami, FL.

Abstract: 

Background: Caspofungin (CancidasTM, MK-0991, L-743,872) is a parenteral antifungal agent that inhibits the synthesis of 1,3 b-D glucan, an essential component of the fungal cell wall. Methods: The potential for drug interactions between caspofungin and tacrolimus (FK-506) was evaluated in a placebo-controlled, randomized, Phase I study. Part (1) was a 2-period, parallel-panel study in which healthy subjects received tacrolimus (2 doses of 0.1 mg/kg oral capsules administered 12 hours apart, n=12) or placebo (n=5) alone in Period 1 and again on Day 10 of caspofungin 70 mg IV daily in Period 2. In Part (2), parallel panels of healthy subjects received tacrolimus (2 doses of 0.1 mg/kg 12 hours apart, n=8) or placebo (n=8) on Days 1 and 10 of caspofungin 50 mg IV daily. Results: The geometric mean ratio (90% CI) for caspofungin plasma AUC(0-24hr) under coadministration relative to administration alone was 1.00 (0.96, 1.04) for Part (1) and 1.05 (0.96, 1.15) for Part (2), based on a mixed-model analysis that evaluated pharmacokinetic data obtained on Days 9 and 10 in both the coadministration and the placebo-control panels. The geometric mean ratio (90% CI) for tacrolimus whole blood AUC(0-12hr) in Period 2 (coadministration) relative to Period 1 (administration alone) was 0.80 (0.72, 0.89) for Part (1), based on a combined analysis of morning and evening doses. Reductions of similar magnitude were also seen for tacrolimus CMAX and C12hr. Conclusions: Tacrolimus does not alter the pharmacokinetics of caspofungin. Caspofungin modestly reduces whole blood concentrations of tacrolimus. For patients receiving both therapies, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended.
2001

abstract No: 

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Full conference title: 

ICAAC 41st
    • ICAAC 41st