Influence of methylxanthines isolated from Bancha green tea on the pharmacokinetics of sildenafil in rats

Background Sildenafil is used to treat erectile dysfunction and pulmonary arterial hypertension and is metabolized in the liver mainly by CYP3A4, thus co-administration with drugs or herbal extracts that affect CYP3A4 activity may lead to drug-drug or drug-herb interactions, respectively. The aim of the present study was to evaluate the influence of single and multiple oral doses of methylxanthine fraction, isolated from Bancha green tea leaves on the pharmacokinetics of sildenafil in rats. Methods Rats were given sildenafil alone as well as simultaneously with methylxanthines or ketoconazole. The plasma concentrations of sildenafil were measured with high-performance liquid chromatography method with ultraviolet detection. The pharmacokinetic parameters of sildenafil were calculated by non-compartmental analysis. Results Concomitant use of sildenafil with a single oral dose of methylxanthines resulted in a decrease in C max ( p > 0.05), AUC 0-t ( p < 0.05) and AUC 0-inf ( p < 0.05), while the administration of sildenafil after methylxanthines pretreatment resulted in an increase in C max ( p < 0.0001), AUC 0-t ( p < 0.0001) and AUC 0-inf ( p < 0.001) compared to the sildenafil group. After co-administration of sildenafil and ketoconazole, a significant increase in C max , AUC 0-t and AUC 0-inf was observed in both of the experiments. Conclusion Drug-herb interactions were observed when sildenafil was co-administered with Bancha methylxanthines in rats. Further in vivo studies about the potential drug interactions between sildenafil and methylxanthines, especially caffeine, are needed to clarify mechanisms underlying the observed changes in sildenafil pharmacokinetics. Graphical abstract