A Randomized, Open-Label, 3-Way Crossover Study to Demonstrate Bioequivalence of Sildenafil Powder for Oral Suspension With Tablets Used Commercially and in Clinical Studies for the Treatment of Pulmonary Arterial Hypertension.

Sildenafil citrate (Revatio) is approved for pediatric pulmonary arterial hypertension (PAH) in the European Union. A new pediatric formulation, 10 mg/mL sildenafil citrate powder for oral suspension (POS), was developed for pediatric PAH patients. Bioequivalence among the POS suspension (20 mg), the Revatio 20-mg commercial tablet, and the sildenafil citrate 2 × 10-mg clinical trial tablets was assessed. In this randomized, open-label study, 42 healthy adult volunteers received the 3 different sildenafil treatments, each in a single 20-mg oral dose, using a 3-way crossover design. Blood samples were collected at predefined times and analyzed for sildenafil plasma concentrations. Natural log-transformed sildenafil pharmacokinetic parameters (Cmax , AUClast , and AUC∞ ) were evaluated for bioequivalence using a mixed-effects model. Results were used to estimate relative bioavailability and construct 90% confidence intervals (CIs). Bioequivalence was concluded if the 90% CIs for Cmax , AUClast , and AUC∞ were wholly contained within 80% to 125%. All 90% CIs for the ratios of adjusted geometric means of Cmax , AUClast , and AUC∞ were within 80% to 125%, the prespecified bioequivalence criteria. All 3 formulations were well tolerated. In conclusion, the POS suspension, the commercial 20-mg Revatio tablet, and the 10-mg sildenafil tablets were all bioequivalent to one another when given at the equal doses.