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
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.
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 Cmax (p > 0.05), AUC0-t (p < 0.05) and AUC0-inf (p < 0.05), while the administration of sildenafil after methylxanthines pretreatment resulted in an increase in Cmax (p < 0.0001), AUC0-t (p < 0.0001) and AUC0-inf (p < 0.001) compared to the sildenafil group. After co-administration of sildenafil and ketoconazole, a significant increase in Cmax, AUC0-t and AUC0-inf was observed in both of the experiments.