A Study of the Effect of Bancha Green Tea Extract and Catechin Fraction on Sildenafil Pharmacokinetics in Rats

Abstract

Background: Sildenafil is a drug that belongs to the group of phosphodiesterase-5 inhibitors. It is used in the treatment of erectile dysfunction and pulmonary arterial hypertension. Sildenafil undergoes metabolism in the liver by CYP3A4 and CYP2C9. Therefore, drug interactions may occur if sildenafil is taken simultaneously with CYP3A4 and CYP2C9 inhibitors such as green tea catechins. Objective: The aim of the present work was to analyze epigallocatechin-3-gallate (EGCG) and caffeine content in total extract and catechin fraction from Bancha green tea leaves as well as to assess their effect on sildenafil pharmacokinetics in rats. Methods: Animals received sildenafil alone and in combination with total Bancha green tea extract, catechin fraction or ketoconazole (a well-known CYP3A4 inhibitor). The plant extracts and the plasma concentrations of sildenafil were analyzed with high-performance liquid chromatography. Results: Administration of sildenafil after pretreatment of the rats with total extract and catechin fraction from Bancha green tea resulted in a statistically significant increase in Cmax, AUC0-t and AUC0-inf and a decrease in the volume of distribution and clearance of sildenafil compared to the control group. A significant increase in Cmax, AUC0-t and AUC0-inf of sildenafil was also observed after simultaneous intake of sildenafil and ketoconazole. Conclusion: Co-administration of sildenafil and the isolated Bancha green tea extracts led to a significant change in sildenafil pharmacokinetics in rats. Therefore, further, in vivo studies are necessary to clarify the exact mechanisms responsible for the interactions established as well as to evaluate the risk for clinically significant interactions in humans.