Pharmacokinetics and bioequivalence of sildenafil granules and sildenafil tablets in Korean healthy volunteers

Background: A sildenafil tablet formulation as a PDE-5 inhibitor is widely used for the treatment of erectile dysfunction. Recently, a fine granular formulation of sildenafil was developed by a domestic Korean pharmaceutical company. Objectives: This study was performed to compare the bioavailability of sildenafil fine granules with that of sildenafil tablets for assessing bioequivalence in 40 healthy male volunteers. Methods: This was an open-label, randomized sequence, single-dose, two-period, and two-treatment crossover study. Half of the volunteers received a single dose of sildenafil fine granule 50 mg and then sildenafil tablet 50 mg after a 7-day washout period. The remaining half of volunteers received the tablet first and then the granule with the same washout period. 10-mL blood samples were serially sampled to measure the concentrations of sildenafil and the N-desmethyl metabolite. Tolerability was assessed during the study. Results: The pharmacokinetic parameters of sildenafil were similar between granular and tablet formulations. The 90% CI of geometric mean ratios (sildenafil granule/tablet) for the pharmacokinetic parameters of sildenafil were within 0.8 - 1.25, as a bioequivalent acceptable range; 1.111 (90% CI, 1.002 - 1.231) for maximum plasma concentration (C-max) and 1.092 (1.019 - 1.117) for area under the concentration-time curve from time zero to time of last measurable concentration (AUC(last)). Also, the 90% CI of geometric mean ratios for C-max and AUC(last) of the metabolite were within 0.8 - 1.25. Both formulations were well tolerated by volunteers. Conclusion: This study confirmed that sildenafil granules and sildenafil tablet are bioequivalent with regards to pharmacokinetics of sildenafil and N-desmethyl sildenafil.