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 the 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 (Cmax) and 1.092 (1.019 - 1.117) for area under the concentration- time curve from time zero to time of last measurable concentration (AUClast). Also, the 90% CI of geometric mean ratios for Cmax and AUClast 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.