Drug Interactions between Caspofungin and Nelfinavir or Rifampin.

J.A. STONE, E. MIGOYA, L. HICKEY, P. DEUTSCH, G. WINCHELL, A, S. BI, R. DESAI, S. DILZER, K. LASSETER, W. KRAFT, H. GREENBERG, S. WALDMAN

Author address: 

Merck Research Labs, West Point, PA, Clinical Pharmacology Assoc., Miami, FL, Thomas Jefferson Univ., Philadelphia, PA.

Abstract: 

Background: Caspofungin (Cancidas™) is an echinocandin antifungal agent. Methods: The potential for drug interactions between caspofungin and nelfinavir or rifampin was evaluated in 2 placebo-controlled, randomized studies. Study A was a 3-panel study in which healthy subjects received 14 days of caspofungin 50 mg IV daily alone (n=10), with nelfinavir 1250 mg twice daily (n=9), or with rifampin 600 mg daily (n=10). Study B was a 2-panel study in which one panel (n=14) received 28 days of rifampin 600 mg daily with caspofungin 50 mg IV daily coadministered on the last 14 days and a second panel (n=12) received 14 days of caspofungin 50 mg IV daily alone. Results: The geometric mean ratio (90% CI) for caspofungin plasma AUC(0 - 24hr) on Day 14 of coadministration relative to administration alone was 1.08 (0.93, 1.26) for nelfinavir, 1.12 (0.97, 1.30) for rifampin (Study A), and 1.01 (0.91, 1.11) for rifampin (Study B). Although caspofungin AUC was not altered by rifampin, the shape of the caspofungin plasma profile was altered, resulting in 14 to 31% reductions in trough (C24hr), consistent with a net induction effect at steady-state. Both AUC and C24hr were elevated in the initial days of rifampin coadministration in Study A (61% and 170% elevations, respectively, on Day 1), but not Study B, consistent with transient net inhibition prior to full induction. The geometric mean ratio (90% CI) for rifampin plasma AUC(0 - 24hr) on Day 14 of coadministration relative to administration alone was 1.07 (0.83, 1.38). Conclusions: Nelfinavir does not meaningfully alter the pharmacokinetics of caspofungin. Caspofungin has no effect on rifampin pharmacokinetics. Rifampin both inhibits and induces caspofungin disposition, resulting in reduced C24hr at steady-state. An increase in the caspofungin dose to 70 mg daily should be considered when coadministered with rifampin.
2003

abstract No: 

A-1605

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd