by Ribeiro I, Blum B, Fernandes J, Santina G, Asada M, Everson M, Schuck E, Feleder E, Evene E, Gualano V. Antimicrobial Agents and Chemotherapy 2021, AAC.02150-19; doi: 10.1128/AAC.02150-19
Summary: E1224, a prodrug of ravuconazole in development for the treatment of mycetoma and Chagas disease, is being investigated for use in combination with other treatments to improve efficacy. The authors assessed the pharmacokinetics and safety interactions of benznidazole, the current standard of care for Chagas disease, and E1224 in healthy volunteers. Ravuconazole had no impact on the pharmacokinetic characteristics of a single oral dose of 2.5 mg/kg benznidazole. At steady state, following concomitant administration of prodrug E1224 with benznidazole, overall ravuconazole exposure significantly increased by about 35%. Both compounds were well tolerated and there were no clinically relevant safety interactions between E1224 and benznidazole. Given these results, co-administration of ravuconazole and benznidazole should not require any adaptation of E1224 dosing.