title: Penetration of SCH-39304, a new antifungal triazole, into cerebrospinal fluid of primates.
abstract: We characterized 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-plasma area under the curve ratio was 0.63 (+/- 0.18, standard error of the mean); maximum concentrations were 1.34 micrograms/ml (+/- 0.18) in CSF and 1.96 micrograms/ml (+/- 0.43) in plasma. The mean plasma half-life was 45.7 h (+/- 11), and mean CSF half-life was 38.7 h (+/- 3.5). The mean levels of SCH-39304 at 24 h were 1.48 micrograms/ml (+/- 0.3) in plasma and 0.96 microgram/ml (+/- 0.12) in CSF. We conclude that SCH-39304 effectively penetrates into CSF and achieves concentrations considered active against many opportunistic yeasts and that these concentrations are sustained in CSF for greater than or equal to 24 h.
authors.affiliation: Section of Infectious Diseases, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: C
authors.initials: C
authors.lastname: Lester-McCully
authors.forename: M G
authors.initials: MG
authors.lastname: Rinaldi
authors.forename: J E
authors.initials: JE
authors.lastname: Wallace
authors.forename: F M
authors.initials: FM
authors.lastname: Balis
authors.forename: J W
authors.initials: JW
authors.lastname: Lee
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
authors.forename: D G
authors.initials: DG
authors.lastname: Poplack
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D006207:Half-Life; D008253:Macaca mulatta; D008297:Male; D014230:Triazoles / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304