Effects of Evodia rutaecarpa and rutaecarpine on the pharmacokinetics of caffeine in rats

To assess possible herb-drug interactions, rutaecarpine (an herbal ingredient of Evodia rutaecarpa; 25 mg/kg/day, p.o.), the ethanol extract of Evodia rutaecarpa (1 g/kg/day, p.o.), and an herbal preparation of Evodia rutaecarpa (Wu-Chu-Yu-Tang; 1 g/kg/day) were individually pretreated daily for three consecutive days in rats and on the fourth day caffeine was administered (2 mg/kg, i.v.). Caffeine concentrations in blood, brain and bile were concurrently measured by microdialysis coupled to a liquid chromatographic system. Pharmacokinetic data were calculated by a non-compartmental model. The results indicate that the caffeine crosses the blood-brain barrier and goes through hepatobiliary excretion. The caffeine level was significantly decreased by the pretreatment of rutaecarpine, the extract of Evodia rutaecarpa and herbal preparation Wu-Chu-Yu-Tang. This finding should be very important whenever herb-drug interactions would be possible for a herbal remedy.