7.1. Caffeine
When rutaecarpine (active indole in Evodia) is fed to rats, the AUC and Cmax values of Caffeine are significantly reduced; meaning rutaecarpine can reduce the exposure of caffeine to the body.[66][67] This also extends to the similar xanthine compound theophylline.[68] These effects extend to consumption of Evodia itself, and combination decoctions such as Wu Zhu Yu Tang.[67]
This effect is rather significant; pretreatment of 80mg/kg oral Rutaecarpine daily for 3 days (a high dose, but its bioavailability is unaugmented) in rats reduced the Cmax to 31% of the control group, the Tmax to 22%, the AUC to 5% of control, and reduced the half-life from 0.73+/-0.07 hours to 0.27+/-0.1 hours.[66] Similar trends were seen for all metabolites of caffeine (paraxanthine, theophylline, theobromine)
Rutaecarpine is able to induce (increase) activity of various hepatic enzymes such as CYP1A2, CYP2B, and CYP2E1;[28][69] CYP2E1 induction is seen at 80mg/kg oral ingestion in rats while only 20mg/kg is needed for CYP1A2.[67] As Caffeine is highly metabolized by CYP1A and CYP2E1, their increased activity causes greater metabolism of caffeine in a shorter time frame and thus limits systemic exposure.
Rutaecarpine appears to potently suppress the circulating levels of caffeine via increasing hepatic and intestinal degradation; a highly antagonistic compound