PMID: 9435196Jan 22, 1998Paper

Lisofylline causes rapid and prolonged suppression of serum levels of free fatty acids

The Journal of Pharmacology and Experimental Therapeutics
S BurstenE Nudelman

Abstract

Lisofylline (LSF), a novel anti-inflammatory compound that modulates stress-associated changes in lipid metabolism, is under development to modify toxicity for patients undergoing dose-intensive cytotoxic therapy for neoplasia and to prevent multiorgan failure and acute respiratory distress syndrome after oxidative injury. The present investigation, a component of a pharmacokinetics study, was performed to assess the effect of LSF on serum-free fatty acids (FFA). LSF was administered at doses of either 1, 2 or 3 mg/kg every 24 hr for 3 days by 10 min intravenous infusion to 12 healthy volunteers, followed 24 hr later by a single oral dose of 6 mg/kg, which was determined not to be bioavailable. Total serum FFA were quantitated after separation from other lipids by thin-layer chromatography in samples from 10 of 12 subjects, and serum levels of individual fatty acids were measured by high-performance liquid chromatography in samples from 11 of 12 subjects. Six hours after the first LSF dose of 1, 2 or 3 mg/kg, FFA levels decreased from the time zero levels by a mean (+/- S.D.) of 64.7 +/- 7.4% (range, 37-80%; P < .001 vs. time zero levels). Six hours after the third i.v. LSF dose, the FFA reached a nadir of 71.5 +/- 5.5% below t...Continue Reading

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