Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events

• Published in: International journal of impotence research Vol. 16; no. S1; pp. S34 - S37
• Main Author: Bischoff, E
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.06.2004
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors; Animals; Bioavailability; Biological Availability; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Evaluation, Preclinical; Drug Interactions; Erectile dysfunction; Humans; Imidazoles - adverse effects; Imidazoles - pharmacokinetics; Imidazoles - pharmacology; Imidazoles - therapeutic use; Intestinal Absorption - drug effects; Male; Nitric Oxide - pharmacology; Penile Erection - drug effects; Pharmacodynamics; Pharmacokinetics; Phosphodiesterase Inhibitors - adverse effects; Phosphodiesterase Inhibitors - pharmacokinetics; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase Inhibitors - therapeutic use; Piperazines - adverse effects; Piperazines - pharmacokinetics; Piperazines - pharmacology; Piperazines - therapeutic use; Purines; Rabbits; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride
• ISSN: 0955-9930; 1476-5489
• DOI: 10.1038/sj.ijir.3901213

Vardenafil potently inhibits human phosphodiesterase 5 (PDE5) with an IC50 of 0.7 nM. Enhancement of nitric oxide (NO)-induced erections in rabbits by 0.1 mg/kg vardenafil is limited by its pharmacokinetic properties (Tmax=1 h; T1/2=1.2 h), although erectile effects have been observed after 7 h. In humans, vardenafil is rapidly absorbed (Tmax approximately 40 min) and more slowly metabolized (T1/2 approximately 4 h), with an absolute bioavailability of 14.5% (vs 40% for sildenafil). Although the consumption of high-fat meals does not affect the drug's relative bioavailability, it retards intestinal absorption. Coadministration of CYP3A4 inhibitors such as ritonavir can affect hepatic metabolism. M1, an active metabolite of vardenafil, is a four-fold-less potent inhibitor of PDE5 than its parent compound, contributing approximately 7% to vardenafil's overall efficacy. The side effects of all selective PDE5 inhibitors commonly include vasodilation, small reductions in blood pressure, headache, and nasal congestion.