The pharmacokinetics of BAY R3783 and its efficacy in the treatment of experimental cryptococcal meningitis

Abstract

We studied the pharmacokinetics and efficacy of BAY R3783, a new antifungal azole compound, in rabbits and compared it with fluconazole and itraconazole. BAY R3783 has at least two active metabolites, BAY U3624 and BAY U3625. We measured serum concentrations of all three compounds; the peak serum level for the parent compound was approximately two hours post dose. BAY R3783 and its metabolites also crossed the blood-CSF barrier; the mean CSF level of BAY R3783 was 30.5% of simultaneous serum levels. The in-vivo activity of the azoles was compared in a model of cryptococcal meningitis in immunosuppressed rabbits. BAY R3783, fluconazole and itraconazole all reduced yeast counts in the CSF with equal efficacy over ten days of therapy at 100 mg/day. In this model, BAY R3783 was effective in the treatment of cryptococcal meningitis.