Pharmacokinetics of a new orodispersible tablet formulation of vardenafil: results of three clinical trials

Clin Drug Investig. 2011;31(1):27-41. doi: 10.2165/11584950-000000000-00000.

Abstract

Background: 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.

Objective: To characterize the pharmacokinetics of a new 10 mg ODT formulation of vardenafil.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Humans
  • Imidazoles / administration & dosage*
  • Imidazoles / adverse effects
  • Imidazoles / pharmacokinetics*
  • Male
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / administration & dosage*
  • Phosphodiesterase 5 Inhibitors / adverse effects
  • Phosphodiesterase 5 Inhibitors / pharmacokinetics*
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Piperazines / pharmacokinetics*
  • Sulfones / administration & dosage
  • Sulfones / adverse effects
  • Sulfones / pharmacokinetics
  • Tablets / administration & dosage*
  • Triazines / administration & dosage
  • Triazines / adverse effects
  • Triazines / pharmacokinetics
  • Vardenafil Dihydrochloride

Substances

  • Imidazoles
  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Sulfones
  • Tablets
  • Triazines
  • Vardenafil Dihydrochloride