Safety and Pharmacokinetics of Higher Doses of Caspofungin.

J. STONE, E. MIGOYA, S. LI, P. DEUTSCH, G. WINCHELL, K. GHOSH, A. MILLER, S. BI, A. BASS, G. MISTRY, R. DAWKINS

Abstract: 

Background: Caspofungin (Cancidasâ„¢, MK-0991) is a parenteral antifungal agent that inhibits the synthesis of 1,3 -D glucan. Previously in the caspofungin clinical program, the highest doses evaluated were 100 mg (single dose) and 70 mg (multiple dose). Methods: The safety, tolerability, and pharmacokinetics of higher doses of caspofungin were evaluated in a 2-part, placebo-controlled, randomized, Phase I study in young healthy adult subjects. In Part (1) serial-panels received single IV doses of 150-mg (n=6, +2 placebo) or 210-mg (n=6, +2 placebo) caspofungin. In Part (2), a single panel received 100-mg caspofungin (n=10) or placebo (n=5) once daily IV for 21 days. Results: Following single doses of 150 mg and 210 mg, geometric mean (GM) AUC(0- ) was 279.66 and 374.92 mcg-hr/mL, respectively, which represent 2.4-fold and 3.2-fold increases, respectively, in exposure over that obtained for a single dose of 70 mg. Half-lives and plasma clearance were similar to historical values for lower doses. Following multiple daily doses of 100 mg, GM Day 14 AUC(0-24hr) was 218.89 mcg-hr/mL, which is 2.5-fold greater than that obtained following multiple daily doses of 50 mg. At 100 mg daily, the AUC accumulation ratio (Day 21/Day 1) was 1.69, which was increased only slightly over that previously obtained at 70 mg daily. Steady state appears to be reached during the third week of dosing. There were no serious clinical adverse experiences (AEs) and no subjects were discontinued due to an AE. The most common AEs were associated with infusion site tolerability. In general, the type of AEs observed in this study had been observed in prior studies with lower doses. Conclusions: Caspofungin, given IV as single 150-mg and 210-mg doses or as multiple daily 100-mg doses, was generally well tolerated. Caspofungin 100 mg daily achieves an exposure approximately 2.5 times that of the currently approved 50-mg daily regimen.
2002

abstract No: 

NULL

Full conference title: 

42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd