LY303366 is an antifungal agent of the echinocandin class with activity against Candida, Aspergillus, and Pneumocystis carinii.

L. NI, B. SMITH, B. HATCHER, M. GOLDMAN, C. MCMILLIAN, M. TURIK, I. RAJMAN, L.J. WHEAT, and V.S. WATKINS

Abstract: 

This open-labeled, single-dose, cross-over study investigated the pharmacokinetics of LY303366 in healthy volunteers and HIV-infected subjects after receiving LY303366 in the morning (AM) and night (PM). Subjects were randomized to receive either an AM or PM dose of 500 mg orally on two separate occasions. The washout period between the two doses was 14 days. No serious adverse events were reported. Two healthy subjects developed mild, transient diarrhea. One HIV-infected volunteer discontinued himself from the study before receiving study drug. LY303366 plasma concentrations were determined by High Performance Liquid Chromatography using ultraviolet detection. Pharmacokinetics of LY303366 were estimated using noncompartmental analysis. The effect of dosing time or status of HIV-infection on the pharmacokinetics of LY303366 were evaluated using mixed effect ANOVA. For both healthy and HIV-infected subjects, LY303366 reached maximum plasma concentration (C_{max}) approximately 6 hours (median value) after receiving the AM dose, and 12 hours (median value) following the PM dose. For healthy volunteers, the mean C_{max} value (with coefficient of variation, CV%) was 372 ng/mL (33.5%) after the AM dose and 359 ng/mL (59.8%) after the PM dose. The mean (CV%) C_{max} value was 302 ng/mL (33.7%) and 403 ng/mL (37.5%) for the HIV-infected subjects after the AM and PM doses, respectively. The C_{max} value was not significantly influenced by dosing time (p=0.39) or status of HIV infection (p=0.80). For healthy volunteers, there were no significant differences (p=0.45) in systemic exposure (measured as AUC) to LY303366 after the AM and PM doses, with an average of 14300 ng*hr/mL (26%) after the AM dose and 17300 ng*hr/mL (54%) after the PM dose. The AUC value for HIV-infected subjects after the PM dose was 18700 ng*hr/mL (39%), which was similar to that for healthy volunteers. However, after HIV-infected subjects received the AM dose, the AUC value was 12700 ng*hr/mL (34%) which was an approximately 33% decrease (p=0.029) compared to that after the PM dose. Results from this study provide valuable information in dose selection for patients in clinical trials.
1998

abstract No: 

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Full conference title: 

38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th