ANALYTICAL AND PHARMACOKINETIC STUDIES WITH AN ANTIVIRAL SULFONE DERIVATIVE (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

ANALYTICAL AND PHARMACOKINETIC STUDIES WITH AN ANTIVIRAL SULFONE DERIVATIVE (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A3179 1992. Unique Identifier : AIDSLINE ICDB/92685714
Bigelow JC; Chrin LR; Mathews LA; McCormack JJ; Dept. of Pharmacology, Univ. of Vermont, Burlington, VT 05405

Abstract: NSC 624231 is a phenyl sulfone derivative (PS) that has demonstrated activity against HIV in vitro. Detection and determination of PS in biological fluids is accomplished by HPLC analysis, using an ODS column and isocratic elution with acetonitrile/water (50/50); biological fluids are processed with acetonitrile prior to HPLC analysis (210 min). Biological studies with PS are complicated by its poor solubility in conventional solvents, but use of a hydroxypropyl beta-cyclodextrin vehicle has permitted the initiation of exploratory pharmacokinetic studies of PS in mice. PS is stable in mouse plasma for periods of up to 48 hr at 37 degrees and shows moderate binding to BSA (50% bound at 0.4% BSA). Iv injection (20 mg/kg) produces peak plasma concentrations of 20 uM with rapid biexponential elimination (half-lives of 2 min and 20 min). Estimates for both Cl (2 ml/min) and Vd (60 ml) were very high, reflecting extremely rapid drug elimination. PS is absorbed after oral administration in the cyclodextrin-based vehicle, but not in simple aqueous suspension; plasma concentrations in the 10-20 uM range are observed for several hours after oral administration (50-200 mg/kg). Exploratory studies with radiolabeled PS have demonstrated rapid conversion to a more polar metabolite(s). For example, analysis of urine samples by both HPLC and TLC indicate that more than 90% of the radiolabel in a given sample is associated with chromatographic fractions well separated from that containing PS.

Keywords: Administration, Oral Animal Antiviral Agents/ADMINISTRATION & DOSAGE/ANALYSIS/PHARMACOLOGY/ *PHARMACOKINETICS Chromatography, High Pressure Liquid Chromatography, Thin Layer Half-Life HIV/DRUG EFFECTS Metabolic Clearance Rate Mice Sulfones/ADMINISTRATION & DOSAGE/ANALYSIS/PHARMACOLOGY/ *PHARMACOKINETICS ABSTRACT
920830
M9281087

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