Metabolic and pharmacokinetic studies on bamifylline. A review

Abstract

The metabolic fate and pharmacokinetics of bamifylline have been investigated by high performance liquid- and gas-chromatography techniques and radio-isotopic methods in several experiments following oral and intravenous administration of single and repeated doses of 300 mg, 600 mg and 900 mg of this drug. The 300 mg single- and multiple-dose experiments were performed by comparing bamifylline with 200 mg of theophylline within the confines of controlled double-blind randomized cross-over studies. Bamifylline is catabolized into several closely related compounds and into sulpho- and glucurono-conjugates of an hydroxylated derivative. Its metabolites are rapidly and extensively excreted via the kidneys and the liver. Only the unchanged bamifylline has been recorded in the blood following administration of the radio-labelled parent compound. Bamifylline achieves peak plasma levels more rapidly than theophylline. The half-life of bamifylline plasma concentrations ranges from 1.5 hours to 2.0 hours, which is appreciably shorter than that of theophylline which exceeds four hours. By further contrast the distribution volumes of bamifylline are three to ten times larger than those of theophylline. No evidence of cumulation has been found in blood following the repeated administration of doses as high as 900 mg administered at intervals of eight hours.