Sildenafil Citrate Kamagra

Sildenafil oral jelly is a selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterases type 5 (PDE5). The physiologic mechanism of erection of the penis involves release of Nitric Oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzymes gyanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of Nitric Oxide (NO) by inhibiting phosphodiesterases type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by Sildenafil causes increase level of cGMP in the corpus cavernosum resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.

In vitro studies have shown that Sildenafil is selective for PDE5, its effect is more potent on PDE5 than on other phosphodiesterases (> 80 – fold for PDE 1, >1000- fold for PDE2, PDE3 and PDE4). The approximately 4,000-fold selectively for PDE5 versus PDE3 is important because that PDE is involved in control of cardiac contractility. Sildenafil is only about 10- fold potent for PDE5 compared to PDE6, an enzyme found in the retina; this lower selectively is thought to be the basis for abnormalities related to colour vision observed with higher doses or plasma levels.

PHARMACOKINETICS

Sildenafil is rapidly absorbed following administration by mouth, with a bioavailability of approximately 40%. Peak plasma concentrations are attained within 30 to 120 minutes; the rate of absorption is reduced when Sildenafil is administered with food.

Sildenafil is widely distributed into tissues and is approximately 96% bound to plasma proteins. It is metabolized in the liver primarily by cytochrome P450 is isoenzymes CYP3A4 (the major route) and CYP2C9. The major metabolite, N-desmethyl-sildenafil, also has some activity. The terminal half-lives of Sildenafil and the N-desmethyl metabolite are about 4 hours.

Sildenafil is excreted, predominantly as metabolites, in the feces, and to a lesser extent the urine. Clearance may be reduced in the elderly and in patients with hepatic or severe renal impairment.

INDICATIONS

Sildenafil is used in the management of erectile dysfunction or impotence in men. Erectile dysfunction signifies inability of a male to achieve satisfactory erection of the penis during sexual intercourse.