Pharmacokinetics of a New Orodispersible Tablet Formulation of Vardenafil

Abstract

Vardenafil is a potent and highly selective oral phosphodiesterase type 5 (PDE-5) inhibitor that has been shown in numerous clinical trials and post-marketing surveillance studies to be safe and effective for improving erectile function in men with erectile dysfunction (ED). Until recently, the drug was only available as a film-coated tablet (FCT). A new orodispersible tablet (ODT) formulation of vardenafil has been developed that disintegrates in the subject's mouth without the need for water or other liquids. To characterize the pharmacokinetics of a new 10 mg ODT formulation of vardenafil. Three clinical trials were conducted: (i) a randomized 4-fold crossover study to assess the effect of food and water on the pharmacokinetics of vardenafil ODT, compared with vardenafil FCT, in healthy men; (ii) a phase I study to assess single and multiple doses of vardenafil ODT, compared with a single dose of vardenafil FCT, in young and elderly men with ED; and (iii) a pharmacokinetic substudy of a phase III trial in men of broad age range with ED. Vardenafil ODT was rapidly absorbed after oral administration without water, with a similar pharmacokinetic profile to vardenafil FCT, except that the ODT exhibited significantly greater bioavailability. After a single dose, the geometric mean area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) of vardenafil ODT increased by 21-44% compared with the FCT. There was no consistent difference in geometric mean maximum vardenafil plasma concentration (C(max)) between the two formulations. Geometric mean AUC(∞) and C(max) were increased by 41% and 24%, respectively, in men with ED aged ≥65 years compared with those aged <65 years. Multiple dosing or administration of vardenafil ODT with food had no meaningful effect on the pharmacokinetics of vardenafil. Vardenafil ODT was well tolerated. Vardenafil ODT should be taken without water. Partial absorption of vardenafil through the oral mucosa results in an unexpected extent of suprabioavailability of the ODT formulation. Vardenafil ODT is a convenient formulation, with pharmacokinetic and safety characteristics that are appropriate for the treatment of ED.