Ravuconazole (RAV) is a long-acting triazole antifungal agent with in vitro activity against a broad spectrum of fungal pathogens, including Candida, Aspergillus, Cryptococcus and key dermatophytic fungi. The present open-label study in 20 healthy subjects was designed to assess the potential for RAV to inhibit CYP3A4, using simvastatin (SIM) as a sensitive marker substrate. On Day 1, subjects received 40 mg SIM. On Day 2, subjects received 400 mg RAV and 40 mg SIM. On Days 3 to 14, subjects received 400 mg RAV once-daily. On Day 15, subjects received 400 mg RAV and 40 mg SIM. Plasma samples were collected over 24 h on Days 1, 2, and 15 to measure SIM concentrations. Concomitant administration of RAV and SIM was well tolerated. No serious adverse events occurred during the study. The AUC for SIM increased 2-fold following a single dose of RAV and only 4-fold following 14 days of dosing with RAV, despite the ~10-fold accumulation of RAV. Since SIM is a very sensitive substrate for CYP3A4 inhibition, the results of this study show that RAV is a less potent inhibitor of CYP3A4 compared to other triazole antifungals which can cause up to a 10-fold increase in AUC for SIM.
Full conference title:
Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 40th