Food effect on pharmacokinetic profiles of sildenafil 100 mg oral films in healthy male volunteers: results from two randomized, single dose, crossover studies

Background: Decades after it was first put on the market, sildenafil is still a very successful treatment for erectile dysfunction. New formulations, such orodispersible films (ODFs), offer more convenience allowing more discreet use and enabling people who might have trouble swallowing tablets to take the drug. Aim: To evaluate the impact of food and water on sildenafil ODF as compared to sildenafil film-coated tablet (FCT) and to assess the safety and palatability of the orodispersible formulation. Methods: Two randomized, single-dose, three-period, crossover studies were conducted on healthy male volunteers. The first study, involving 45 subjects, was designed to compare ODF versus FCT under fasting conditions and to study the effect of high-fat, high-calorie meal on ODF pharmacokinetic (PK) profiles. The second study, involving 35 subjects, compared ODF versus FCT under fed conditions and the effect of water on ODF PK profiles. Blood samples were collected within 24 h post-dosing to measure plasma sildenafil and its metabolite, N-desmethyl-sildenafil. Outcomes: Primary outcomes were maximum observed plasma concentration (C max), the area under the concentration-time curve (AUC), and the time of maximum observed plasma concentration (T max). Secondary outcomes included palatability and safety. Results: Food delayed sildenafil 100 mg ODF T max by 1.45 h and decreased C max by 45% but did not affect the extent of systemic exposure to sildenafil (AUC). Bioequivalence was demonstrated for sildenafil ODF administered with and without water under fed conditions. C max of plasma sildenafil was ~13% and 17% lower for ODF (without and with water, respectively), and T max was delayed by 1-1.5 h, compared to FCT under fed conditions, but both AUC0-t and AUC0-∞ met the bioequivalence limits. Palatability was acceptable with mild aftertastes. The ODF formulation was well-tolerated with no severe adverse events. Clinical implications: Sildenafil ODF is a bioequivalent alternative to traditional tablets. The food impact on sildenafil ODF taken with and without water is consistent with that associated with FCT, influencing C max and T max but not AUC. Strengths and limitations: The study population consisted exclusively of healthy subjects, and the study was limited to single-dose administration. Lastly, although bioequivalence of PKs implies therapeutic equivalence, future studies incorporating clinical endpoints would offer more conclusive evidence of interchangeability. Conclusion: Sildenafil ODF has comparable PKs and added convenience for patients. Its versatility, ease of use, and discreetness make it ideal as safe and effective alternative to FCT.ISRCTN registry numbers where the trial protocols can be accessed:Study A: ISRCTN13297409 (10.1186/ISRCTN13297409)Study B: ISRCTN15394603 (10.1186/ISRCTN15394603).