Vardenafil hydrochloride(Levitra) powder video
Vardenafil hydrochloride(Levitra) powder Characters:
Vardenafil is a white or off-white crystalline powder, odorless, bitter, soluble in water and ethanol.
|Name:||Vardenafil hydrochloride(Levitra) powder|
|Metabolism Hepatic (CYP3A4)|
|Elimination half-life 4–5 hours|
Vardenafil is a phosphodiesterase inhibitor PDE5 used to treat impotence ( erectile dysfunction ) and is marketed under the name of Levitra ( Bayer AG ) and Vivanza ( GSK ). Developed by Bayer, Germany, and first listed in the US in 2002. It is ten times more powerful than sildenafil.
The PDE-5 inhibitor suppresses the action of the enzyme called PDE-5 involved in erection in the corpus cavernosa and exerts its effect by acting on the NO-operated nerve in the periphery of the penis to dilate blood vessels and promote blood flow to encourage sustainability of erection.
Simple description of the product
Vardenafil is very popular due to immediate effect, strong erectile power, prolongation of ejaculation time, few side effects. For the general public there is no problem, but dialysis patients, for example, are contraindicated to take only Vardenafil formulation. Also, there is no indication for people over 65 years old.
In addition to the ED treatment effect of vardenafil, an extension effect of ejaculation time is known as a secondary effect. The effect of prolonging the ejaculation time is not examined in Vardenafil 5 mg and the effect of prolonging the ejaculation time is recognized with a significant difference at 10 mg or more. This is an unrecognized effect for sildenafil which is a component of Viagra, tadalafil which is a component of Cialis. There is a report that the time to ejaculation when continuing sexual activity without taking rest from after insertion of 10 mg of vardenafil has been extended from approximately 49 seconds to 83 seconds and reports that it extended from 36 seconds to 7.5 minutes but a side effect Even though it does not extend the ejaculation time of all people.
It turns out that if it becomes ED and the hardness of the penis decreases, the sensitivity increases and the ejaculation time gets faster. For that reason, it is important to take Levitra for premature ejaculation of ED merger to keep firm penis hardness, to use dapoxetine preparation of premature ejaculation drug (Prelizy, Posetto etc.) together, many are satisfied with combination of Vardenafil and Dapoxetine You will be able to do sexual intercourse.
Pharmacological action and mechanism of action
During sexual stimulation, neurons and vascular endothelial cells in the corpus cavernosum release nitric oxide NO and activate soluble guanylate cyclase, resulting in the formation of cyclic guanosine cGMP. A series of biochemical reactions are then stimulated, which ultimately causes relaxation of the smooth muscle of the penile artery. A decrease in vascular tone leads to an increase in penile blood flow and a swelling of the cavernous tissue.
The swollen corpus cavernosum compresses the vein between the corpus cavernosum and the tunica albuga, causing a decrease in blood exudation and an increase in intracavernous pressure, resulting in penile erection. PDE5 is a member of the family of cyclic nucleotide hydrolases capable of hydrolyzing second messenger cGMP. A total of 11 PDEs are known, and PDE5 is the major cGMP hydrolase in the human corpus cavernosum.
When NO is released during sexual stimulation, inhibition of PDE5 can increase the level of cGMP in the penis, thereby enhancing the action of endogenous NO; NO and cGMP are at a low level in the presence of asexual stimulation, so sexual stimulation is PDE5 inhibition. The necessary conditions for the agent to work.
Vardenafil is rapidly absorbed after oral administration, reaching maximum plasma concentration (C max ) in the fasting state for 15 minutes , peak time (T max ) 90% is 30-120 minutes (average 60 minutes) ). The average absolute bioavailability of oral vardenafil is approximately 15% due to the significant first-pass effect. At the recommended dose of 5 – 20 mg, after oral vardenafil, the increase in AUC (area under drug concentration-time curve) and Cmax was almost proportional to the dose increase. When vardenafil was ingested with a high-fat diet (57% lipid content), the absorption rate of vardenafil was reduced, Tmax was prolonged by 60 minutes, and Cmax was reduced by an average of 20%, but AUC was not affected. When vardenafil was ingested at the same time as the normal diet (30% fat), its pharmacokinetic parameters (C max , T max , and AUC) were not affected. Therefore, vardenafil and food can be taken together or alone.
The average volume of distribution of vardenafil to steady state is 208 L. Vardenafil and its main active metabolite, M1, are highly associated with human plasma proteins (approximately 95%) and this binding is independent of the total concentration of the drug and is reversible. After 90 minutes of taking vardenafil in healthy volunteers, the concentration of the drug in the semen does not exceed 0.00012% of the dose.
Vardenafil is mainly metabolized by the liver enzyme system CYP3A4 type, and a small part is metabolized by CYP3A5 and CYP2C9 isoenzymes. The plasma elimination half-life of vardenafil is approximately 4-5 hours. The main circulating metabolite (M1) of vardenafil in the body is derived from piperazine citrate deethylation, and then M1 continues to metabolize. The plasma elimination half-life of M1 is similar to the prototype drug, which is about 4 hours. In the systemic circulation, part of M1 is a bound glucuronide. The M1 of non-glucuronide in plasma accounts for about 26% of the original drug component. The metabolite M1 has a phosphodiesterase selectivity similar to vardenafil. In vitro, M1 inhibits PDE5 by about 28% of vardenafil, accounting for 7% of the drug.
The total clearance rate of vardenafil in the body is 56 liters/hour, and its terminal half-life is 4-5 hours. After oral administration, vardenafil is excreted as a metabolite, mostly excreted in the feces (91-95%) and a small fraction excreted in the urine (2-6%).
Use of the product
Treatment of male erectile dysfunction
Valdenafil is a first-line treatment for erectile dysfunction in the treatment of male erectile dysfunction. Developed by Bayer, Germany, and first listed in the US in 2002. Like sildenafil, it is a second-generation type 5 phosphodiesterase inhibitor that works very quickly and works for about 15 to 20 minutes. It is ten times more powerful than sildenafil. Clinical data show that 50% to 60% of men with diabetes over 50 years of age have erectile dysfunction, and erectile dysfunction caused by neurological and vascular damage caused by diabetes is particularly difficult to treat. The potent selective phosphodiesterase 5 (PDE5) inhibitor vardenafil developed by Bayer may bring good news to patients with erectile dysfunction caused by diabetes. These drugs are used as a one-time treatment drug. After oral administration for about 1 hour before sex, the concentration of CGMP is reduced by selective inhibition of PDE5, and the release of cGMP induced by nitric oxide (NO) released after sexual stimulation is increased. Smooth muscles for enhanced erectile function.
Dosage of the product
Vardenafil as Levitra has 5 mg, 10 mg, 20 mg formulation. The usual dose is 10 mg and it is the quickest in comparison with sildenafil and tadalafil. It takes effect in about 10 to 30 minutes after taking the effect. Beginning in 10 to 30 minutes after taking the dose, the blood concentration reaches its peak at 45 minutes after taking and the effect lasts about 5 to 8 hours after taking it. It is also the ingredient with the strongest erection strength. Sildenafil is less frequent in side effects compared to sildenafil and it is an improved version of sildenafil.
The recommended starting dose is 10 mg, taken approximately 25-60 minutes before sexual intercourse. In clinical trials, taking 4-5 hours before sexual intercourse, it still shows efficacy. The maximum recommended dose is used once a day. Vardenafil can be taken with or with food. Sexual stimulation is required as an instinctive response for treatment.
The dose can be increased to 20 mg or reduced to 5 mg depending on the efficacy and tolerability. The maximum recommended dose is 20 mg per day.
Dose of liver dysfunction:
Mild liver dysfunction, no need to adjust the dose; moderate liver dysfunction, the recommended starting dose is 5mg, and then gradually increase to 10mg according to efficacy and drug resistance; severe liver function Incomplete, the dose is not clear.
No dose adjustment is required in patients with mild, moderate, or severe renal impairment. Vardenafil pharmacokinetic studies in dialysis patients have not been conducted.
The simultaneous administration of vardenafil and alpha-blockers in some patients may result in symptomatic hypotension. Only when the patient is treated with an alpha blocker to stabilize the condition can the drug be combined. For patients with stable disease with alpha-blockers, the dose of vardenafil should be 5 mg of the minimum recommended starting dose and tamsulosin can be taken at any time. When vardenafil is combined with other alpha-blockers, there should be some intermittent doses. For patients who have taken the optimal dose of vardenafil, the use of alpha-blockers should start with the lowest dose. For patients taking PDF5 inhibitors (including vardenafil), an increase in the dose of alpha blocker may cause a further drop in blood pressure in the patient.
1. It can be used together with CYP 3A4 inhibitors (such as ritonavir, indinavir, saquinavir, ketoconazole, itraconazole, erythromycin, etc.) to inhibit the metabolism of the drug in the liver. The blood concentration is increased, the half-life is prolonged, and the incidence of adverse reactions (such as hypotension, visual changes, headache, facial flushing, and abnormal penile erection) increases. This medicine should be avoided in combination with ritonavir and indinavir. When combined with erythromycin, ketoconazole, and itraconazole, the maximum dose of this drug does not exceed 5mg, and the dose of ketoconazole and itraconazole must not exceed 200mg.
2. Patients taking nitrates or receiving nitric oxide donors should avoid using this drug. The mechanism of action is to further increase the concentration of cGMP, resulting in increased antihypertensive effect and increased heart rate. Used together with the alpha blocker, it can enhance the antihypertensive effect and lead to hypotension, so it is forbidden to use this drug for those who are using alpha blockers. The medium fat diet (30% fat calorie) has no significant effect on the pharmacokinetics of a single oral dose of 20 mg. The high fat diet (more than 55% fat fat) can prolong the peak time of the drug and reduce the blood concentration of the drug.
When erythromycin is used at the same time, the maximum dose of vardenafil does not exceed 5 mg. When taking ketoconazole or itraconazole, the maximum dose of vardenafil should not exceed 5 mg. When the dose of ketoconazole and itraconazole exceeds 200 mg, vardenafil cannot be taken. Avoid taking the potent CYP3A4 inhibitors indinavir and ritonavir at the same time.
Vardenafil’s adverse reactions are usually transient, and mostly mild to moderate, patients can usually be well tolerated. The most common adverse reactions are mainly headache, facial flushing and nasal congestion, which is also a typical adverse reaction of PDE5 inhibitors.
1. Effects on blood pressure: All PDE5 inhibitors have a slight vasodilating effect, which causes a small decrease in blood pressure, and vardenafil is no exception. The study showed that the ED patients had a slight decrease in transient blood pressure from 1 to 5 hours after oral administration of vardenafil 5 to 20 mg. The mean systolic blood pressure decreased by 1. 4 to 6. 6 mmHg, and the diastolic blood pressure decreased by 2. 0 to 4.8. mmHg. This reduction in blood pressure is small and generally has no clinical significance. Studies have shown that vardenafil 5 mg, 10 mg, and 20 mg are equally well tolerated in patients with ED who receive antihypertensive drugs for hypertension. There were no significant differences in systolic blood pressure, diastolic blood pressure, and heart rate between the vardenafil group and the placebo group. Despite this, it is generally not recommended to take antihypertensive drugs or alpha 1 blockers in the treatment of benign prostatic hyperplasia at the same time taking the above drugs and PDE5 inhibitors.
2. Studies on the effects of cardiac repolarization (QT/QTc interval) have confirmed that vardenafil has no significant effect on the QT/QTc interval. This was a placebo-effective (moxifloxacin, therapeutic dose) control, a double-blind study of six treatment regimens, evaluating 58 healthy men (mean age 53 years) with a single oral vardenafil 10 mg 80 Effects of mg, sildenafil 50 mg and 400 mg, moxifloxacin 400 mg, and placebo on QT/QTc interval. The results showed that vardenafil did not increase the absolute QT interval, only slightly prolonging the QTc interval (10 mg therapeutic dose and 80 mg super-therapeutic dose of vardenafil extended the QTc interval by 4-10 msec) to the extent of That is not similar. These QTc changes have no obvious clinical significance. There was no correlation between the dose of vardenafil and the QTc interval. Based on the results of this study, the US FDA believes that vardenafil does not cause significant arrhythmias in clinical use.
Because sexual activity is associated with a degree of cardiac risk, doctors should first consider their heart condition before taking any treatment for an erectile dysfunction. The vasodilator properties of vardenafil may result in a temporary mild decrease in blood pressure. Patients with left ventricular dysfunction, such as aortic stenosis and idiopathic hypertrophic aortic stenosis, may be sensitive to vasodilator drugs, including PDE5 inhibitors. Because of the potential for cardiac risk, heart disease patients are not recommended for sexual intercourse, so medications for treating erectile dysfunction are often not available.
For patients with anatomical malformations of the penis (eg, angulation, cavernous fibrosis, Peyronie’s disease), or penile erections that cannot resolve (eg, sickle cell disease, multiple myeloma, and leukemia), treatment of erectile dysfunction is required Use medication with caution.
The safety and efficacy of vardenafil has not been studied in combination with other methods of treating erectile dysfunction and is therefore not recommended for use.
It has been reported that transient blindness and non-arteritic anterior ischemic optic neuropathy are associated with the use of Elida and other PDE5 inhibitors. Patients should be advised to stop taking Elida in the event of sudden blindness and seek medical attention immediately.
Vardenafil is not used in patients with active bleeding or peptic ulcer activity and should only be used after a careful benefit-risk assessment.
When vardenafil is used alone or in combination with aspirin, there is no effect on bleeding time.
In vitro tests of human platelets have shown that vardenafil alone does not inhibit platelet factor-induced platelet aggregation. During the overdose treatment, vardenafil was observed to slightly enhance the anticoagulant effect of sodium nitroprusside and nitric oxide donors in a concentration-dependent manner. Vardenafil combined with heparin had no effect on bleeding time in rats, but its interaction was not studied in humans.