sm-8668 and Meningitis

The triazole SCH39304 was compared with itraconazole and fluconazole for treatment of murine coccidioidal meningitis. Mice were treated for 30 days with 1, 5, 10, or 30 mg of each drug per kg of body weight. Survival and brain tissue counts were measured. At equivalent doses, SCH39304 was more effective than the other triazoles.

Topics: Animals; Antifungal Agents; Coccidioidomycosis; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Fluconazole; Itraconazole; Ketoconazole; Meningitis; Mice; Mice, Inbred BALB C; Triazoles

We studied the pharmacokinetics and in vivo antifungal action of SCH39304, a new antifungal azole compound, in rabbits. It crossed the blood-cerebrospinal fluid barrier in the presence or absence of meningeal inflammation, reaching approximately 60% of the simultaneous concentrations in serum. In the treatment of experimental cryptococcal meningitis, SCH39304 was as effective as fluconazole in reducing yeast counts in the subarachnoid space. SCH39304 and fluconazole both were highly effective against candida endophthalmitis, sterilizing the vitreous humor and the choroid and retina. SCH39304 suppressed candida endocarditis and reduced yeast counts in the kidney at all doses tested. SCH39304 was effective in the treatment of experimental cryptococcal meningitis and disseminated candidiasis. Further investigations in humans are warranted.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Meningitis; Microbial Sensitivity Tests; Rabbits; Triazoles