PENETRATION OF SCH-39304, A NEW ANTIFUNGAL TRIAZOLE, INTO CEREBROSPINAL-FLUID OF PRIMATES

We characterize the cerebrospinal fluid (CSF) penetration and pharmacokinetics of SCH-39304 in adult rhesus monkeys receiving a single oral dose of SCH-39304 (2.0 mg/kg of body weight). The mean CSF-to-lasma area under the curve ratio was 0.63 (± 0.18, standard error of the mean); maximum concentrations were 1.34 μg/ml (± 0.18) in CSF and 1.96 μg/ml (± 0.43) in plasma. The mean plasma half-life was 45.7 (± 0.3) in plasma and 0.96 μg/ml (± 0.12) in CSF. We conclude that SCH-39304 effectively penetrates into CSF and achieves concentrations considered active against many opportunistic yeast and that these concentrations are sustained in CSF for ≥ 24 h.