Torfin 100mg Bal Pharma drugs treat erectile dysfunction (1 blister x 4 tablets)

Pharmacokology

The characteristics of the learning force

Torfin is a oral medication to treat erectile dysfunction, rehabilitation of weak erection function, causing natural response when sexually stimulated.

Mechanism of action

The physiological mechanism of the erection is due to the release of Nitrogen II Oxyd (NO) and the cave when there is sexual stimulation. After that, nitrogen II Oxyd activated the enzyme Ganylate Cyclase, resulting in increased guanosin monophosphate (CGMP), relaxing the cave smooth muscles and increasing blood flow into the cave.

Sildenafil is a selective and strong inhibitor for enzymes phosphodiesterase, which is specific 5 specific on CGMP (PDE5), this enzyme broke CGMP in the cave. Thus, Sildenafil has indirect effect on the penis.

Sildenafil has no direct relaxation effect on the isolated human cave, but promotes the exhaust effect of NO on this tissue. When the No/CGMP road is activated by sexual stimulation, PDes inhibitors by Sildenafil increases the CGMP level in the cave. Therefore, sexual stimulation should be stimulated for Sildenafil to have favorable pharmacological effects.

The only dose of oral Sildenafil is up to 100 mg in healthy volunteers does not cause clinical effects on the electrocardiogram. The maximum reduction in systolic blood pressure in the posture after taking 100 mg Sildenafil is 8.4 mmHg. The corresponding change of diastolic blood pressure in the lying position is 5.5 mmHg. This hypoglycemia corresponds to the vasodilation effect of Sildenafil, perhaps due to an increase in CGMP concentration in blood vessel plain muscle.

Sildenafil does not affect the sensitivity and the contrast of vision. Mild and transient changes in color distinctions (green/green) are discovered in some people using Farnsworth-Munsell 100 color tests, 1 hour after taking Sildenafil 100 mg, there is no evidence after 2 hours of medication.

The mechanism of a distinctive change of color is related to Sildenafil's inhibition to PDE6, an isenzyme related to the chain of reactions to the light of the retina. In vitro studies show that Sildenafil has an impact on PDE5 10 times stronger on PDE6.

In vitro studies have shown Sildenafi's selection on PDE5 more powerful than 10-10000 times compared to other PDE forms (PDE 1, 2, 3, 4 and 6). Specifically, the selection of PDE5 is 4,000 times stronger than PDE3, PDE3 is the specific phosphodiesterase isomer on the Camp involving the control of myocardial contraction.

pharmacokinetics

Sildenafil is metabolized in the liver (mainly at Cytochrom P450 3A4) and its metabolites have the same activity as the mother (Sildenafil).

On In vitro, the concentration of 3.5 nm Sildenafil inhibits the PDE5 enzyme of the person about 50%, on humans, the maximum free Sildenafil concentration after using a single dose of 100 mg is approximately 18 ng/ml or 38 Nm.

absorption

Sildenafil is quickly absorbed after drinking, with absolute bioavailability of about 40% (ranging from 25 - 63%) and achieving an average maximum concentration in plasma from 30 - 120 minutes (an average of 60 minutes). High fat foods reduce Sildenafil's absorption capacity with an average decrease time in TMAX to 60 minutes and CMAX decreased by 29%average.

distribution

Sildenafil's average drug distribution (VSS) is 105 l, which focuses on tissues. Sildenafil and the metabolites in its large circulatory round are N-Desmethyl mounted up to 96% to plasma proteins. The attachment to plasma protein does not depend on its total concentration. Sildenafl's concentration in semen of healthy volunteers after taking 90 minutes is less than 0.0002% of the dose of use (average 188 mg).

transformation

Sildenafil is metabolized mainly by CYP3A4 (main roads) and CYP2C9 (sub -line) in the liver. The metabolites in the main metabolic ring of Sildenafl generated from the n-Desmethyl chemical process and then further metabolized.

These metabolites have a selective activity for PDE similar to Sildenafil and on Vitro selective in PDE5 approximately 50% of the mother. The plasma concentration of metabolites is approximately 40% of the mother concentration. N-Desmethyl metabolites are metabolized again, with a half-life of 4 hours.

Elimination

Sildenafil's entire clearance 41 l/h with half phase time is 3-5 hours. After oral or intravenous use, Sildenafil is excreted mainly in the form of metabolic substances (about 80% of oral dose) and a small part through the urine (about 13% of oral dose).

pharmacokinetics in special patients

Older people

On healthy elderly people (from 60 years of age), Sildenafil's clearance decreases and its free plasma concentration is larger in healthy young people (aged 18 to 45) is approximately 40%. Many studies show that age does not affect the unwanted effect rate.

Renal failure

On people with mild kidney failure (Creatinine clearance = 50 - 80 ml/min) or average (Creatinine clearance = 30 - 49 ml/minute), when using a single dose of Sildenafil (50 mg), there is no change in pharmacokinetics.

On severe people (creatinine clearance

People with liver failure

On people with cirrhosis (Child A, Child B), Sildenafil's clearance is reduced, the result increases the area under the AUC curve (84%) and CMAX (47%) compared to people without liver failure.

Caution when using

Caution with patients with severe liver and kidney failure, reducing the dose of Sildenafil if necessary.

Be careful when prescribing erectile dysfunction agents for patients with deformations of penis anatomy (such as angle folding penis, caves fibrosis, or Peyronie disease), patients with pathological diseases that cause penis pain (such as sickle cell anemia, multiple marrow disease, leukemia).

If the erection lasts more than 4 hours, patients should see a doctor due to penis tissue damage and lose the erection ability of the penis later.

Patients should stop using Sildenafil and go to the doctor in case of hearing loss or sudden vision.

Sildenafil should not be used for patients with blindness 1 eye with optic neuropathy due to anemia in the front area without artery causes regardless of whether it is related to the use of drugs inhibitors in the previous type 5 or not.

Patients with a history of dizziness or visual disorders should not drive or operate machinery. Because there may be some risks of heart -related heart activity may occur, the physician must pay attention to the patient's cardiovascular condition before the treatment of erectile dysfunction.

There is no Sildenafil's safety evidence in patients with severe liver failure, hypertension, hypotension, a history of stroke, myocardial infarction, life -threatening heart attack, unstable angina, heart failure or retinal disorders such as pigmentitis (a small number of patients with retinitis with nest retinitis with phosphodiesterase gene disorders in the retina). Sildenafil should not be used for these groups of patients.

Means a history and meticulous clinical examination to diagnose erectile dysfunction, to identify potential causes and determine appropriate treatment.

Through some clinical trials, Sildenafil has a systemic vasodilation property that causes transient hypotension. For most patients, it has very little or no effect. However, before prescribing, physicians must pay attention to patients with pathological conditions that may be affected by this effect and especially when they have more sexual activity.

Patients who hinder the left ventricular flow (for example, aortic stenosis, obstructive hypertrophy of myocardial disease) or suffer from syndrome of multiple system atrophy are patients with hyperactive hyperplasia, manifested by a serious decline in the ability to control blood pressure automatically, those who need to be very considerate when treatment.

Safety and effectiveness of Sildenafil coordination with other drugs to treat erectile dysfunction is not studied, so it is not coordinated with the treatment of these drugs, and in vitro studies on human platelets shows that Sildenafil has an effect on platelet anti -platelets of sodium nitroprussid (substance for nitric oxid).

There is no safe information about the use of Sildenafil in patients with acute blood clotting or digestive ulcers, so be cautious in these patients.

The ability to drive and operate machines

There is no recommendation of the influence of the drug on driving and operating machinery.

Pregnancy

Do not take medicine for women.

Research on rats and rabbits after taking oral Sildenafil, not seeing evidence of monitoring, reducing fertility, or adverse effects for embryo and fetal development. There are no complete and appropriate studies on pregnant women.

Breastfeeding period

There are no adequate and appropriate studies on breastfeeding women.

Drug interaction

The effect of other drugs on Sildenafil

In vitro studies

Metabolism of Sildenafil takes place mainly by cytochrom P450 (CYP) groups 3A4 (main road) and 2C9 (sub -line). Therefore, all agents that inhibit these groups reduce the clearance of Sildenafil.

In vivo studies

Mobile pharmacokinetic analysis through clinical test data shows that when using Sildenafl simultaneously with CYP3A4 inhibiting agents (such as erythromycin, ketoconazole, cimetidin) will reduce Sildenafil's clearance. Cimetidine (800 mg) is a non -specific inhibitor, when used with Sildenafil (50 mg), it will increase the concentration of sildenafl in plasma to 56% on healthy people.

erythromycin (500 mg used 2 times daily for 5 days) is a special inhibitor agent CYP3A4, when used simultaneously with a single dose of 100 mg Sildenafil, increasing the area under the Sildenafil curve (AUC) up to 182%.

In addition, simultaneously using a single dose of 100 mg Sildenafil with the protease inhibitor of HIVinavir (1,200 mg used 3 times daily), this is also a CYP3A4 inhibitor agent, increasing Sildenafil's CMAX up to 140% and increasing AUC to 210%.

Sildenafil has no effect on saquinavir pharmacokinetics (see the dose and usage). The more powerful CYP3A4 inhibitors such as Ketoeonazole and Itraconazole will also have greater effects.

Single -dose of 100 mg Sildenafil with HIV Ritonavir (500mg, use 2 times daily) increased Sildenafil's CMAX by up to 300% (4 times) and increased AUC in plasma up to 1000% (11 times).

The time 24 hours after using the drug, the concentration of Sildenafl in plasma is still approximately 200 ng/ml compared to 5 ng/ml when Sildenafil alone. This indicates a clear impact of ritonavir on P450.

Sildenafil had no effect on Ritonavir's pharmacokinetics. (See the dose and usage).

When using Sildenafil for patients who are treating the potential inhibiting agents CYP3A4, as recommended, the free Sildenafil concentration in plasma must not exceed 200 Nm and must be well tolerated.

Single dose of antacids (magnesium hydroxid, aluminum hydroxid) does not affect the bioavailability of Sildenafil.

Through the dynamic data on clinical trials, the agents inhibit CYP2C9 (such as Tolbutamid, Wafarin), CYP2D6 inhibitors (such as Serotonin Rehabilitation Inhibitors, 3 -round antidepressants), Thiniazide Administration, Angiotensin (ACE) enzyme inhibitors that do not affect Canxi Sildenafil's dynamics.

On healthy men who volunteered, there was no effect of azithromycin (500 mg daily for 3 days) to AUC, CMAX, Tmax, elimination, Sildenafil's cancellation time as well as transformed in its main path.

Do not use Sildenafil with grape juice due to increased plasma sildenafil concentrations. CYP3A4 induction substances such as rifampicin reduce the concentration of sildenafil. Bosartan also reduces the exposure to Sildenafil.