Open AccessPenetration of SCH-39304, a new antifungal triazole, into cerebrospinal fluid of primates
Author(s) -
Thomas J. Walsh,
Cynthia M. Lester-McCully,
Michael G. Rinaldi,
Jack Wallace,
Frank M. Balis,
J W Lee,
P A Pizzo,
David G. Poplack
Publication year - 1990
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.34.6.1281
Subject(s) - cerebrospinal fluid , pharmacokinetics , penetration (warfare) , microgram , half life , area under the curve , chemistry , plasma concentration , body weight , pharmacology , endocrinology , medicine , in vitro , biochemistry , operations research , engineering
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.
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