| Indication |
Used for the treatment of erectile dysfunction |
| Pharmacodynamics |
Vardenafil is used to treat male erectile dysfunction
(impotence) and pulmonary arterial hypertension (PAH). Part of the
physiological process of erection involves the release of nitric oxide
(NO) in the corpus cavernosum. This then activates the enzyme guanylate
cyclase which results in increased levels of cyclic guanosine
monophosphate (cGMP), leading to smooth muscle relaxation in the corpus
cavernosum, resulting in increased inflow of blood and an erection.
Vardenafil is a potent and selective inhibitor of cGMP specific
phosphodiesterase type 5 (PDE5) which is responsible for degradation of
cGMP in the corpus cavernosum. This means that, with vardenafil on
board, normal sexual stimulation leads to increased levels of cGMP in
the corpus cavernosum which leads to better erections. Without sexual
stimulation and no activation of the NO/cGMP system, vardenafil should
not cause an erection. |
| Mechanism of action |
Vardenafil inhibits the cGMP specific phosphodiesterase type 5
(PDE5) which is responsible for degradation of cGMP in the corpus
cavernosum located around the penis. Penile erection during sexual
stimulation is caused by increased penile blood flow resulting from the
relaxation of penile arteries and corpus cavernosal smooth muscle. This
response is mediated by the release of nitric oxide (NO) from nerve
terminals and endothelial cells, which stimulates the synthesis of cGMP
in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and
increased blood flow into the corpus cavernosum. The inhibition of
phosphodiesterase type 5 (PDE5) by vardenafil enhances erectile function
by increasing the amount of cGMP. |
| Absorption |
Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%. |
| Volume of distribution |
|
| Protein binding |
95% |
| Metabolism |
Vardenafil is metabolized predominantly by the hepatic enzyme
CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major
circulating metabolite, M1, results from desethylation at the piperazine
moiety of vardenafil. M1 shows a phosphodiesterase selectivity profile
similar to that of vardenafil and an in vitro inhibitory potency for
PDE5 28% of that of vardenafil. |
| Route of elimination |
After oral administration, vardenafil is excreted as metabolites
predominantly in the feces (approximately 91-95% of administered oral
dose) and to a lesser extent in the urine (approximately 2-6% of
administered oral dose). |
| Half life |
4-5 hours |
| Clearance |
|
| Toxicity |
Symptoms of overdose include vision changes and back and muscle pain. |
