Pharmacological Properties Of Vardenafil Hydrochloride

Brief introduction
Valdenafil hydrochloride is a first-line treatment for erectile dysfunction in men. Developed by Bayer AG in Germany, it was first listed in the United States in 2002. Like sildenafil, it belongs to the second generation of type 5 phosphodiesterase inhibitor, which takes effect very quickly, about 15-20 minutes. The effect is ten times stronger than sildenafil. Clinical data show that 50%~60% of male diabetes patients over 50 years old suffer from erectile dysfunction, and erectile dysfunction caused by nerve and blood vessel damage caused by diabetes is particularly difficult to treat.
Adverse reactions
As a one-time therapeutic drug, after oral administration about one hour before sexual life, the concentration of cGMP is increased by selectively inhibiting the effect of PDE5, blocking the degradation of cGMP induced by nitric oxide (NO) released after sexual stimulation, relaxing arterial smooth muscle, enhancing erectile function, and occasionally having adverse reactions such as headache, blushing, stomach discomfort, color vision disorder, etc.
Mechanism of action
Three selective phosphodiesterase type 5 (PDE5) inhibitors: sildenafil, vardenafil hydrochloride and tadalafil are first-line drugs for the treatment of ED; In terms of drug efficacy, safety, and tolerability, there was no significant difference between PDE5 inhibitors and apomorphine; Injecting prostaglandin E1 into the sponge is a second line treatment method for ED; The effectiveness of intraurethral administration of prostaglandin E1 is slightly worse than that of intracavernous injection of prostaglandin E1. The conclusion is that PDE5 inhibitors have the characteristics of effectiveness, good tolerance, and safety in the treatment of ED; The treatment methods of apomorphine, intracavernous injection of prostaglandin E1, and intraurethral administration of prostaglandin E1 are also effective and well tolerated.
Biological activity
Vardenafilhydrochloride is a highly selective, oral active, and effective phosphodiesterase 5 (PDE5) inhibitor with an IC50 of 0.7nM. Vardenafilhydrochloride has selectivity for PDE1 (180nM), PDE6 (11nM), PDE2, PDE3, and PDE4 (>1000nM). Vardenafilhydrochloride non competitively inhibits the hydrolysis of cyclic guanosine phosphate (cGMP), thereby increasing cGMP levels. Vardenafilhydrochloride can be used to study erectile dysfunction.

Pharmacological properties
Vardenafil enhances the natural response to sexual stimulation by inhibiting the degradation of cGMP by phosphodiesterase type 5 (PDE5) in the human penile sponge, increasing the release of endogenous nitric oxide in the sponge under sexual stimulation.
Vardenafil is a highly selective PDE-5 enzyme inhibitor that primarily exerts therapeutic effects by specifically inhibiting the activity of PDE-5 enzymes, leading to penile erection. Compared with similar products, this drug has the characteristics of fast onset, sustained and reliable efficacy, high erection quality, and good safety. After taking vardenafil, the clinical report showed that 35% of the patients took effect in 15 minutes, the effective rate in 30 minutes to 1 hour was 81%, and the half-life was equal to sildenafil. Compared with sildenafil and silex (tadanafil), vardenafil has advantages and disadvantages in PDE-5 inhibitors: the IC50 of tadanafil, the PDE-5 inhibitor, is 0.9 nM `~6.7 nM, and the IC50 of vardenafil is 0.1 Nm~0.7 nM. Obviously, vardenafil has 5 times more inhibitory capacity on PDE-5 than sildenafil. The selective binding ability of PDE-5 inhibitors to other PDE isoenzymes (such as PDE1-4, PDE7-10, and PDE-5) is not significantly different, but exists for PDE-6.
Matters needing attention
1. Patients with allergic symptoms to any component of the drug (active or inactive) are prohibited.
2. Similar to the mechanism of action of PDE inhibitors in the NO/cGMP pathway, PDE5 inhibitors may enhance the antihypertensive effect of nitrate drugs. Therefore, patients taking nitrate or nitric oxide donor therapy should avoid using vardenafil simultaneously.
3. Avoid the simultaneous use of HIV protein kinase inhibitors indinavir or ritonavir and vardenafil, as they are powerful CYP3A4 inhibitors.