translation agency

Penetration of fluconazole into cerebrospinal fluid following administration of high doses to AIDS patients with cryptococcal meningitis.
Gatti G; Menichetti F; Tosti A; Marroni M; Miletich F; Travaini S;
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:158. Unique

Current experience on fluconazole (F) for cryptococcal meningitis in AIDS patients (pts) is based on doses lower than 10 mg/kg/day (400-600 mg/day for induction and 200-400 mg/day for maintenance therapy). However, it can be hypothesized that higher doses may be associated to improved clinical outcome. To verify this hypothesis, we administered F for induction therapy of cryptococcal meningitis at doses greater than 10 mg/kg to 14 AIDS pts. The dosage regimen was subsequently reduced for maintenance therapy. Concomitant samples of cerebrospinal fluid (CSF) and serum were obtained from 13 pts at different time intervals and dosage regimens during treatment. Serum and CSF were obtained 5 times in 2 pts, 3 times in 4 pts, 2 times in 5 pts e 1 time in 2 pts. Approximately 1/3 of the samples was obtained following i.v. administration while 2/3 following oral administration. Levels of F, determined by HPLC, were as Follows:(Table: See Text). Concentrations of F increased linearly and significantly with respect to the administered dose (serum: p = 0.006, CSF: p = 0.003, Kruskal - Wallis). Our study provides a pharmacokinetic base to the possibility of administering F at high doses to AIDS pts with cryptococcal meningitis.

Acquired Immunodeficiency Syndrome/*COMPLICATIONS Antifungal Agents/ADMINISTRATION & DOSAGE/BLOOD/*CEREBROSPINAL FLUID/THERAPEUTIC USE Chromatography, High Pressure Liquid Dose-Response Relationship, Drug Fluconazole/ADMINISTRATION & DOSAGE/BLOOD/*CEREBROSPINAL FLUID/ THERAPEUTIC USE Human Meningitis, Cryptococcal/*DRUG THERAPY ABSTRACT