Buy Primaxetin (Dapoxetine) 6 tabs 30mg online. Free worldwide shipping.
Brand: JSC FP "Obolenskoye"
Drug form: Film-coated tablets
Manufacturers: Russia, Moscow region
Active substance: Dapoxetine hydrochloride
Group: To increase potency
Expiration date: 3 years
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PRIMAXETIN (Dapoxetine) 6 tabs 30mg
Indications for use of Primaxetin (Dapoxetine) are:
Treatment of premature ejaculation in men from 18 to 64 years old.
Pharmachologic effect:
Pharmacological action - preventing premature ejaculation.
Pharmacodynamics:
It is assumed that the mechanism of action of dapoxetine during premature ejaculation is associated with inhibition of serotonin reuptake by neurons, followed by an increase in the action of a neurotransmitter on pre- and postsynaptic receptors.
The mechanism of ejaculation is regulated mainly by the sympathetic nervous system. The stimulus that triggers ejaculation is generated in the spinal reflex center, which is controlled through the brain stem by several nuclei of the brain, incl. preoptic and paraventricular. Postganglionic sympathetic nerve fibers innervate the seminal vesicles, the vas deferens, the prostate gland, the muscles of the urethra, and the bladder neck, causing them to contract in a coordinated manner to achieve ejaculation. Dapoxetine affects the ejaculation reflex, increasing the latency period and reducing the duration of reflex impulses of perineal ganglion motor neurons.
Pharmacokinetics:
Suction. Dapoxetine is rapidly absorbed, and Cmax in blood plasma is reached within 1–2 hours after taking the drug. The absolute bioavailability is 42% (range 15–76%). After a single oral intake of dapoxetine on an empty stomach in doses of 30 and 60 mg, the Cmax of the substance in the blood plasma is 297 ng / ml (after 1.01 hours) and 498 ng / ml (after 1.27 hours), respectively.
Eating fatty foods moderately reduces the Cmax of dapoxetine (by 10%) and increases the AUC and Tmax in blood plasma by 12%. However, the degree of absorption of dapoxetine does not change. These changes are not clinically significant. Primaxetin® can be taken with or without food.
Distribution. More than 99% of dapoxetine binds to plasma proteins in vitro. The active metabolite, desmethyldapoxetine, binds to blood plasma proteins by 98.5%. Dapoxetine is rapidly distributed throughout the body with an average Vss of 162 liters. With intravenous administration in humans, the average T1 / 2 in the initial, intermediate and terminal phases of excretion is 0.1; 2.19 and 19.3 hours, respectively.
Metabolism. In vitro studies suggest that dapoxetine is metabolized by many liver and kidney enzymes, especially CYP2D6, CYP3A4 and renal flavin-containing monooxygenase (FMO1). In a clinical study in which the metabolism of 14C-dapoxetine was studied, dapoxetine after oral administration was actively metabolized mainly by N-oxidation, N-demethylation, hydroxylation of the naphtho group, glucuronization and addition of a sulfo group. After oral administration, signs of presystemic metabolism in the liver were found. The main components circulating in the blood plasma were intact dapoxetine and dapoxetine N-oxide. In vitro studies have found that dapoxetine N-oxide is inactive. In addition, desmethyldapoxetine and didezmethyldapoxetine were detected in an amount of less than 3% of the total circulating dapoxetine metabolites. In an in vitro study, it was found that desmethyldapoxetine is comparable in activity to dapoxetine, and didesmethyldapoxetine is approximately 2 times less active than dapoxetine. The exposure (AUC and Cmax) of unbound desmethyldapoxetine was 50 and 23% of unbound dapoxetine, respectively.
Excretion. Dapoxetine metabolites are excreted mainly in the urine as conjugates. The unchanged active substance is not detected in the urine. Dapoxetine is rapidly excreted, as evidenced by the low concentration of the substance in the blood plasma (less than 5% of the maximum) 24 hours after the dose. With daily intake, the accumulation of the substance in the body is minimal. When taken orally, the final T1 / 2 is approximately 19 hours.
Special patient groups
Race. A single dose of dapoxetine in a dose of 60 mg did not reveal a statistically significant difference in indicators in Europeans, blacks, Hispanics and Mongolians. Comparison of the pharmacokinetics of dapoxetine in Europeans and Japanese showed higher Cmax and AUC values, in the latter (by 10–20%) due to their lower body weight. A higher level of systemic exposure is unlikely to cause a significant difference in clinical effect.
Special patient groups
Race. A single dose of dapoxetine in a dose of 60 mg did not reveal a statistically significant difference in indicators in Europeans, blacks, Hispanics and Mongolians. Comparison of the pharmacokinetics of dapoxetine in Europeans and Japanese showed higher Cmax and AUC values, in the latter (by 10–20%) due to their lower body weight. A higher level of systemic exposure is unlikely to cause a significant difference in clinical effect.
Elderly age (65 and older). A single dose of dapoxetine at a dose of 60 mg did not reveal a significant difference in pharmacokinetic parameters (Cmax, AUC, Tmax) in healthy elderly men and younger men. The mean AUC values of dapoxetine and the final T1 / 2 were higher by 12 and 46%, respectively, in older men compared with younger men.
Impaired renal function. A single dose of dapoxetine at a dose of 60 mg did not reveal a relationship between Cl creatinine and Cmax or AUC of dapoxetine in patients with weak (Cl creatinine 50-80 ml / min), moderately expressed (Cl creatinine from 30 to <50 ml / min) and severe ( Cl creatinine <30 ml / min) impaired renal function. The AUC of dapoxetine in patients with severe renal impairment was approximately 2 times higher than in patients with normal renal function. Data on the use of the drug in patients with severe renal impairment are limited. In patients requiring hemodialysis, the pharmacokinetics of dapoxetine have not been studied.
Liver dysfunction. In patients with mild liver dysfunction, the pharmacokinetics of dapoxetine and desmethyldapoxetine did not change. In patients with moderate hepatic dysfunction (Child-Pugh class B), the Cmax and AUC of unbound dapoxetine are increased by 55 and 120%, respectively. The Cmax of the unbound active fraction of dapoxetine was unchanged, and the AUC was doubled. In patients with severely impaired liver function, the Cmax of unbound dapoxetine was not changed, and the AUC of unbound dapoxetine was increased by more than 3 times. The AUC of the active fraction was also increased several times.
CYP2D6 polymorphism. The concentration of dapoxetine in blood plasma after a single dose of Primaxetin® at a dose of 60 mg in patients with low CYP2D6 activity was higher than in patients with high CYP2D6 activity (Cmax - by about 31%, AUC - by about 36%). Similarly, the Cmax of desmethyldapoxetine in patients with low CYP2D6 activity was increased by 98%, and AUC - by 161%. The mean endpoint T1 / 2 of dapoxetine is increased by 2.4 hours in patients with low CYP2D6 isoenzyme activity compared with patients with high CYP2D6 isoenzyme activity. Cmax of the active fraction of dapoxetine increased by 46%, and AUC - by 90%. This increase may be accompanied by an increased frequency and severity of dose-related adverse events. The safety of using Primaxetin® in patients with low CYP2D6 activity may raise doubts while taking other drugs that can inhibit the metabolism of dapoxetine, in particular active and moderately active CYP3A4 inhibitors.
It is expected that in patients with ultra-high activity of CYP2D6, the concentration of dapoxetine and desmethyldapoxetine in blood plasma will be reduced.