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

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.

• Authors: Roland Heinig, Boris Weimann, Hartmut Dietrich, Michael-Friedrich Böttcher
• Journal: Clinical drug investigation (Clin Drug Investig) Vol. 31 Issue 1 Pg. 27-41 ( 2011) ISSN: 1173-2563 [Print] New Zealand
• PMID: 20925442 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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