Cialis

Pharmacodynamics

Tadalafil is an effective reversible selective inhibitor of specific phosphodiesterase type 5 (PDE5), cyclic guanosine monophosphate (cGMP). When sexual stimulation causes local release of nitric oxide, inhibition of PDE5 tadalafil leads to increased levels of cGMP in the cavernous body of penis.The result is relaxation of smooth muscles of arteries and blood flow to the tissues of the penis, causing an erection. Tadalafil has no effect in the absence of sexual stimulation.

Studies in vitro have shown that tadalafil is a selective inhibitor of PDE5. PDE5 is an enzymefound in the smooth muscles of cavernous bodies in vascular smooth muscle of internal organs, skeletal muscle, platelets, kidney, lung, and cerebellum. Effects of tadalafil for PDE5 is more active than other phosphodiesterase. Tadalafil is 10 000 times more potent for PDE5 than for FDE1, FDE2, PDE4 and FDE7,which are located in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle and other organs. Tadalafil 10 000 times more active blocks PDE5 than FDE3 — an enzyme that is found in the heart and blood vessels. This selectivity for PDE5 compared to FDE3 is important,FDE3 as an enzyme participating in the reduction of the heart muscle. Additionally, tadalafil is approximately 700 times more potent for PDE5 than for FDE6 found in the retina and is responsible for fotoperedachu.Tadalafil is also showing the action in 9000 times more potent for PDE5 compared with its effect on FDE8, 9 and 10 and 14 times more potent for PDE5 compared to FDE11. Tissue distribution and physiological effects of inhibiting FDE8 — FDE11 has not yet been clarified.Cialis improves erection and the possibility of successful sexual intercourse. The drug acts within 36 hours. The effect is manifested within 16 minutes after taking the drug in the presence of sexual arousal.Tadalafil in healthy individuals does not cause significant changes in systolic and diastolic blood pressure compared with placebo in the supine position (mean maximum decrease of 1.6 / 0.8 mm Hg. Art., Respectively) and in the standing position (mean maximum decrease of 0, 2/4, 6 mm Hg. Art., respectively).Tadalafil does not cause significant changes in heart rate. Tadalafil does not cause changes in recognition of colors (blue / green), due to its low affinity to FDE6. In addition, there is no effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size.Tadalafil does not cause changes in testosterone, luteinizing hormone and follicle-stimulating hormone in the blood plasma.

There were no clinically significant effect on the characteristics of sperm in men who took daily doses of tadalafil for 6 months in placebo-controlled studies.

Pharmacokinetics

AbsorptionAfter oral administration of tadalafil is rapidly absorbed. The average maximum concentration (Cmax) in plasma is reached after an average of 2 hours after ingestion.

The rate and extent of absorption of tadalafil are not dependent on food intake, and the drug Cialis can be taken regardless of meals.Hours (morning or evening) had no clinically significant effect on the rate and extent of absorption.

The pharmacokinetics of tadalafil in healthy individuals is linear with respect to time and dose. In the dose range of 2.5 to 20 mg of the area under the curve «concentration-time» (AUC) increases proportionally to the dose.Equilibrium plasma concentrations are reached within 5 days while taking the drug once and day.

The pharmacokinetics of tadalafil in patients with impaired erectile function is similar to the pharmacokinetics of the drug in patients without erectile dysfunction.

Distribution

The average volume of distribution is about 63 liters, which indicatesthat tadalafil is distributed into body tissues. At therapeutic concentrations, 94% of tadalafil in plasma is associated with proteins. Protein binding is not affected by impaired renal function.

In healthy persons less than 0.0005% of the administered dose was found in semen.

MetabolismTadalafil is mainly metabolized by CYP3A4 isozyme, with the participation of cytochrome P450. The major circulating metabolite is metilkateholglyukuronid. This metabolite, at least 13,000 times less potent for PDE5 than tadalafil. Consequently, the concentration of this metabolite is not clinically significant.

BreedingIn healthy individuals the average clearance tadalafil ingestion of 2.5 l / h and the average half-life — 17.5 hours. Tadalafil is excreted mainly in the form of inactive metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).

Special Populations

Elderly patientsHealthy elderly (65 years and over) had a lower clearance of tadalafil when taken orally, which was reflected in the increase in area under the curve «concentration-time» by 25% compared with healthy individuals aged 19 to 45 years. This difference is not clinically significant and does not require dose adjustment.Patients with renal insufficiency

In patients with renal insufficiency, including patients on hemodialysis, the area under the curve «concentration-time» was greater than in healthy individuals.

Patients with liver failure

The pharmacokinetics of tadalafil in patients with low and medium-severe hepatic impairment is comparable to that in healthy individuals. For patients with severe hepatic impairment (classified Child-Pugh Class C) data are not available.

Patients with diabetes mellitus

In patients with diabetes during treatment with tadalafil area under the curve «concentration-time «was less than about 19% lower than in healthy individuals. This difference does not require dose adjustment.

Indications for use

Erectile dysfunction.

Contraindications
Established hypersensitivity to tadalafil or to any substance, part of the drug;
In the case of taking the drugs,containing any organic nitrates;
The use by persons under 18 years of age.

Precautions

Since there is no data in patients with severe hepatic impairment (classified Child-Pugh Class C), caution must be exercised in the appointment of Cialis this group of patients.Caution must be exercised in the appointment of Cialis to patients taking alpha-[1]-blockers such as doxazosin, since the simultaneous use can lead to symptomatic hypotension in some patients. In clinical pharmacology studies in 18 healthy volunteers who received a single dose of tadalafilsymptomatic hypotension was not observed with concomitant administration of tamsulosin, an alpha [1A]-blocker (see «Interaction with other medicinal products»).

Dosage and administration

For oral administration.

The maximum recommended dose of Cialis is 20 mg.Cialis is taken before anticipated sexual activity, regardless of the meal. The drug should be taken at least 16 minutes before anticipated sexual activity.

Patients may attempt to carry out sexual intercourse at any time within 36 hours after dosing forto establish the optimal response time to receive the drug.

The maximum recommended frequency of administration — once a day.

Side effect

The most frequently reported adverse events were headache and dyspepsia (11 and 7%, respectively). Adverse events associated with taking tadalafilwere usually small or medium severity, transient and decreased with continued use of the drug.

Other common adverse effects include back pain, myalgia, nasal congestion and «tides» of blood to the face.

Rarely — edema of the eyelids, eye pain, conjunctival hyperemia, and dizziness.

Very rarely -hypersensitivity reactions (including rash, urticaria and facial edema, Stevens-Johnson syndrome and exfoliative dermatitis), hypotension (patients who have already received antihypertensive drugs), hypertension, syncope, abdominal pain and gastroesophageal reflux, hyperhidrosis (excessive sweating); priapism erection and delay;Blurred vision, no arterial anterior ischemic optic neuropathy, retinal vein occlusion, impaired visual field.

Myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations and tachycardia observed in patients who previously had cardiovascular risk factors.However, it is impossible to pinpoint whether these phenomena directly with these risk factors, with tadalafil, sexual excitement, or a combination of these or other factors.

Overdose

In a single assignment healthy persons tadalafil at a dose of 500 mg and patients with erectile dysfunction (many times up to 100 mg per day)adverse effects were the same as when using lower doses. In case of overdose should be carried out standard symptomatic treatment. In hemodialysis tadalafil virtually no output.

Interaction with other medicinal products

The influence of other drugs on tadalafilTadalafil is mainly metabolized by the enzyme CYP3A4. Selective inhibitor of CYP3A4, ketoconazole (400 mg per day) increases the impact of a single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketokonazop (200 mg per day)increases the impact of a single dose of tadalafil (AUC) by 107% and Cmax by 15% with respect to AUC and Cmax values ​​for only one of tadalafil.

Ritonavir (200 mg twice daily), an inhibitor of CYP3A4, 2C9, 2S1E and 2D6, increases the impact of a single dose of tadalafil (AUC) by 24% without changing the C max. Although thethat the specific interactions have not been studied, we can assume that other HIV protease inhibitors such as saquinavir, and SURZA4 inhibitors such as erythromycin and itraconazole, increase the activity of tadalafil.

Selective inducer of CYP3A4, rifampin (rifampicin, 600 mg per day)reduces the impact of a single dose of tadalafil (AUC) by 88% and Cmax by 46%, with respect to AUC and Cmax values ​​for only one of tadalafil. It can be assumed that the simultaneous administration of other inducers of CYP3A4 should also reduce the concentration of tadalafil in plasma.Simultaneous treatment with an antacid (magnesium hydroxide / aluminum hydroxide) and tadalafil reduced the rate of absorption of tadalafil without altering the area under the curve for tadalafil.

Increasing the pH of the stomach as a result of receiving H2-antagonist nizatidina, had no effect on the pharmacokinetics of tadalafil.
Buy Cialis

Posted on 08.02.2012, in Медицина and tagged , , , , , , , , , , , , . Bookmark the permalink. Оставьте комментарий.

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