Herb-Drug Interaction ofPaullinia cupana(Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats

Paullinia cupanais used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified)Paullinia cupanaextract and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose ofPaullinia cupana(821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.), and in a second study rats were pretreated during 14 days withPaullinia cupana(821 mg/kg/day, p.o.) receiving amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose). Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were measured and analysed. A significant reduction in the peak plasma concentration (73.2%) and in the extent of systemic exposure (57.8%) to amiodarone was found in rats simultaneously treated withPaullinia cupanaand amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction betweenPaullinia cupanaextract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats.