The pharmacokinetics of Signature Cobra Vega in the recommended dose range is linear.

Suction. After intake of Vega Extra is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Vega Extra Cobra 120 at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of PDE-5 50%. After a single dose of Vega Extra Cobra 120 100 mg average Cmax free Sildenafil Vega Extra 120 in plasma men is about 18 ng/ml (38 nm). Cmax when taking Vega Extra Cobra 120 inside fasting is achieved for an average of 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the rate of absorption decreases: Cmax decreases by an average of 29%, and Tmax increases by 60 minutes, but the degree of absorption does not change significantly (AUC decreases by 11%).

Distribution. The average Vss of Vegah Extra 130 is 105 l. the Association of Vega Extra Cobra 120 and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose of Sildenafil Vega Extra 120 (an average of 188 ng) was found in sperm 90 minutes after taking the drug.

Metabolism. Vegah Extra 120 Indication is metabolized mainly in the liver by the action of CYP3A4 isoenzyme (main pathway) and CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite, formed as a result of N-demethylation of Vegah Extra 130, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vega Extra Cobra 120, and its activity against PDE-5 in vitro is about 50% of the activity of Vega Extra Cobra 120. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of Cobra Vega 120. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.

Breeding. The total clearance of Cobra Vega 120 Mg is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Vega Extra Cobra 120 is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).

Clinical data

Cardiac studies. The use of Vega Extra Cobra 120 in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers. The maximum decrease in systolic pressure in the supine position after taking Vega Extra Cobra 120 at a dose of 100 mg was 8.3 mm Hg.art., and diastolic pressure — 5.3 mm Hg.a More pronounced, but also transient effect on blood PRESSURE was observed in patients taking nitrates (see "Contraindications" and "Interaction").

In a study of the hemodynamic effect of Vega Extra Cobra 120 in a single dose of 100 mg in 14 patients with severe coronary artery disease (more than 70% of patients had stenosis of at least one coronary artery), systolic and diastolic resting pressure decreased by 7 and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Cobra 120 Vega Extra did not affect cardiac output and did not interfere with blood flow in stenotic coronary arteries, and also led to an increase (by about 13%) of adenosine-induced coronary flow in both stenotic and intact coronary arteries. In a double-blind placebo-controlled study of 144 patients with erectile dysfunction and stable angina, taking antianginal drugs (except nitrates), exercise was performed until the severity of symptoms of angina increased. The duration of the exercise was significantly longer (19.9 seconds; 0.9–38.9 seconds) in patients taking Vega Extra Cobra 120 in a single dose of 100 mg, compared with patients receiving placebo.

In a randomized double-blind placebo-controlled study, the effect of changing the dose of Cobra Vega (up to 100 mg) in men (n=568) with erectile dysfunction and hypertension, taking more than two antihypertensive drugs, was studied. Cobra 120 Vega Extra improved erection in 71% of men compared to 18% in the placebo group. The frequency of adverse effects was comparable to that in other groups of patients, as well as in those taking more than three antihypertensive drugs.

Studies of visual impairment. In some patients, 1 h after taking Vega Extra Cobra 120 at a dose of 100 mg with the Farnsworth-Mansell test 100 revealed a slight and transient violation of the ability to distinguish shades of color (blue/green). After 2 hours after taking the drug, these changes were absent. It is believed that color vision impairment is caused by inhibition of PDE-6, which is involved in the process of color transmission in the retina. Vega Extra Cobra 120 had no effect on visual acuity, contrast perception, electroretinogram, IOP or pupil diameter.

Vegab Extra is a potent selective inhibitor of cGMP-specific PDE-5.

Mechanism of action

The implementation of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, the subsequent relaxation of smooth muscle tissue of the cavernous body and an increase in blood flow.

Vegah Cobra does not have a direct relaxing effect on the isolated cavernous human body, but enhances the effect of nitric oxide by inhibiting PDE-5, which is responsible for the disintegration of cGMP.

Selective Vegah Extra 120 Indication against PDE5 in vitro, its activity against PDE5 superior activity against other known PDE isoenzymes: PDE-6 — 10 times; PDE-1 more than 80 times; PDE-2, PDE-4, PDE-7 PDE–11 more than 700 times. Vega Extra Cobra 120 is 4000 times more selective for PDE-5 than PDE-3, which is crucial because PDE-3 is one of the key enzymes in the regulation of myocardial contractility.

A prerequisite for the effectiveness of Vegah Extra 120 Mg is sexual stimulation.

Vega Extra Cobra 120 restores impaired erectile function in conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.

Cardiovascular complications

During the post-marketing use of Vega Extra Cobra 120 for the treatment of erectile dysfunction, adverse events such as severe cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) were reported, which had a temporary connection with the use of Cobra Vega 120. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events were observed shortly after sexual activity, and some were observed after taking Sildenafil Vega Extra 130 without subsequent sexual activity. It is not possible to establish a direct link between the reported adverse events and those or other factors.

Hypotension

Vega Extra Cobra 120 has a systemic vasodilating effect, leading to a transient decrease in blood PRESSURE, which is not clinically significant and does not lead to any consequences in most patients. However, before prescribing Vega Extra Cobra 120, the doctor should carefully assess the risk of possible undesirable manifestations of vasodilating action in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the output tract of the left ventricle (aortic stenosis, GOCMP), as well as with the rare syndrome of multiple systemic atrophy, manifested by a severe violation of the regulation of blood PRESSURE from the autonomic nervous system.

Since the combined use of Vega Extra Cobra 120 and α-blockers can lead to symptomatic hypotension in some sensitive patients, Vega Extra Cobra should be used with caution in patients taking α-blockers (see "Interaction"). To minimize the risk of postural hypotension in patients taking α-blockers, the drug Vega Extra Strong 120 should be started only after achieving stabilization of hemodynamic parameters in these patients. It should also consider reducing the initial dose of Vegah Extra 120 Indication (see. "Dosage and administration"). The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

Cobra Vega Extra Strong 120 Mg