Effects of Paullinia cupana (Guarana) seed extract on the systemic exposure of amiodarone in rats

M Rodrigues1,2, C Canário3, M Matias3, J Abrantes1,2, A Ferreira3, G Alves2,3, A Falcão1,2. 1Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal, 2CNC – Centre for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal, 3CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal

Paullinia cupana, commonly known as Guarana, is a climbing evergreen vine with small fruits native to the Amazon region. The high caffeine content and stimulating properties of Paullinia cupana extract makes it particularly attractive in weight loss programs; it may help to increase the metabolic rate and thermogenesis. Therefore, considering the relationship between obesity and cardiovascular diseases, this work was designed to assess the potential for an herb-drug interaction among a standardized Paullinia cupana seed extract and amiodarone (a cardiovascular drug with narrow therapeutic index) in Wistar rats.

On the day preceding treatment, a lateral tail vein of each rat was cannulated, under anaesthesia [ketamine (90 mg/kg)/xylazine (10 mg/kg), i.p. injection], by insertion of an indwelling cannula used for serial blood sampling. In the following day, adult male Wistar rats (n=6) were simultaneously co-administered with a single-dose of Paullinia cupana (821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.) by gavage. Rats of the control group (n=6) were administered with the corresponding volume of vehicle of the extract instead of extract suspension. Blood samples were collected at 0.25, 0.5, 1, 2, 4, 6, 8, 12 and 24 h after dosing; the last blood sampling was taken by decapitation and exsanguination under anaesthesia. Additionally, several tissues (heart, liver, kidneys and lungs) were also harvested at 24 h post-dose. Then, plasma and tissue concentrations of amiodarone and mono-N-desethylamiodarone (major metabolite of amiodarone) were further quantified by a previously developed and validated HPLC-DAD method.

The non-compartmental pharmacokinetic analysis of the plasma concentration-time data revealed a significant decrease in the peak plasma concentration of amiodarone in the rats administered with Paullinia cupana extract comparatively to those of the control group (0.370 ± 0.043 µg/mL vs. 1.378 ± 0.179 µg/mL, p<0.001); in addition, a remarkable reduction of the systemic exposure to amiodarone was observed in the experimental group comparatively to the control group (5.387 ± 0.619 μg.h/mL vs. 12.774 ± 0.688 μg.h/mL, p<0.001). In all tissues was also observed a significant decrease in the concentrations of amiodarone and mono-N-desethylamiodarone in the group of rats treated concomitantly with Paullinia cupana extract and amiodarone.

To the best of our knowledge, these results demonstrated for the first time an herb-drug interaction between Paullinia cupana extract and amiodarone, which determined a considerable decrease on the bioavailability of amiodarone in rats. Therefore, the therapeutic efficacy of amiodarone may be impaired in patients taking amiodarone concomitantly with herbal medicinal products having in their composition Paullinia cupana seed extract.

Acknowledgements : Fundação para a Ciência e a Tecnologia (SFRH/BD/61901/2009; SFRH/BPD/46826/2008), Portugal.