An animal model for the detection of drug-induced inhibition of caffeine metabolism

Abstract

Plasma levels of caffeine are increased more than 400% in rats given furafylline (10 mg kg-1 p.o.) and caffeine (25 mg kg-1 p.o.) as compared to rats given caffeine alone. In rats given idrocilamide (100 mg kg-1 p.o.) and caffeine (25 mg kg-1 p.o.) accumulation of xanthine is higher than 600%. The chromatographic separation and analysis of plasma extracts indicates that the N3-demethylation pathway is inhibited. Since furafylline and idrocilamide have been shown to increase blood levels of caffeine by the same mechanisms in humans and to give rise to adverse reactions, the rat would appear to be a suitable model to detect and study the inhibition of the metabolism of caffeine by such drugs and could be usefully included in the usual series of drug interaction studies done routinely during drug development.