The broad spectrum antifungal triazole SCH 56592 has extremely poor aqueous solubility. Since a large proportion of patients who develop systemic infections cannot tolerate oral therapy, an intravenous formula is necessary. SCH 59884, a phosphate ester prodrug of SCH 56592, is inactive in vitro. However, SCH 59884 is dephosphorylated in vivo to an intermediate ester, SCH 207962, which is then hydrolyzed to SCH 56592. SCH 207962 and SCH 56592 were active in vitro (NCCLS methodology, mcg/ml) against 30 strains of Aspergillus (Asp) and 109 of Candida (Cand). In time-kill studies against a C. krusei strain, SCH 207962 and SCH 56592 were active at concentrations as low as 0.125 Âµg/ml. In experimental pulmonary Aspergillus and systemic Candida infections, mice treated with either SCH 59884 (PD50s, 7.1 and 0.8 mg/kg, respectively) or SCH 56592 (5.5, 0.2) had similar survival results, suggesting that SCH 59884 is converted to its active forms in vivo.
Full conference title:
39th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 39th