Vardenafil pharmacokinetics is almost proportional to the dose within the recommended range. vardenafil 20mg rapidly absorbed orally. The absolute bioavailability - 15%. 30-120 minutes (median 60 minutes) - In healthy volunteers, single doses of 20 mg administered TMAH. As a fatty foods with 18-50% of the administered HAMC (based on 2 studies) will be reduced.
The volume of distribution at steady state vardenafil 20mg - 208 L, indicating extensive tissue distribution. vardenafil 20mg and its major metabolite - M1 - also bound to plasma proteins (approximately 95%) is bound, the binding is reversible and not dependent on the total concentration of drugs.
In healthy subjects, single doses of oral vardenafil 20mg 20 mg, 0.00018% of the dose was recovered in semen 1.5 hours after ingestion.
vardenafil 20mg is metabolized primarily in the liver primarily by CYP3A4 and CYP3A5 isoforms and CYP2S. The main metabolite M1 is formed by piperazine deetilirovaniya vardenafil 20mg. The concentration of M1 in plasma is approximately 26% of that of vardenafil 20mg. On the selectivity of the metabolite is similar to vardenafil 20mg.
The combined use of potent CYP3A4 inhibitors such as ritonavir, indinavir, ketoconazole, itraconazole, and with an inhibitor of the average force - erythromycin - resulting in a significant increase in plasma levels of vardenafil (see "Interactions", "Dosage and Administration ").
The total clearance of vardenafil - 56 l / h, the terminal T1 / 2 of vardenafil and M1 - approximately 4-5 hours after vardenafil is metabolized primarily via the faeces (approximately 91-95% of an oral dose) and a lesser amount in the urine (approximately 2% -6 secreted).
Vardenafil is metabolized primarily in the liver, with the participation of CYP3A4, but also with the participation of a number of isoenzymes CYP3A5 and CYP2C9. As potent inhibitors of these enzymes (cimetidine, ketoconazole, itraconazole, indinavir, ritonavir), vardenafil clearance, while the use of these drugs do not exceed the maximum dose of 5 mg of vardenafil should / day.
In an application with the CYP3A4 inhibitor erythromycin is the recommended maximum dose of vardenafil 10 mg / day.
Concomitant use of vardenafil with alpha-blockers may develop symptomatic hypotension. Therefore, vardenafil 5 mg, 10 mg and 20 mg may not be earlier than 6 hours after administration of alpha-blockers are administered.
Concomitant administration of heparin in rats and vardenafil had no effect on bleeding time. The effect of this combination on bleeding time in humans has not been studied.
Because PDE inhibitors have an effect on the system of nitric oxide / cGMP, PDE5 inhibitors may potentiate the hypotensive effect of nitrates to increase.
In studies with human platelets in vitro have shown that vardenafil not only platelet aggregation induced by various platelet agonists inhibit. Vardenafil use in therapeutic doses, a slight increase in a dose-dependent effect of sodium antiagregatsionnogo - a drug that a nitric oxide donor.
Since safety and efficacy of vardenafil in combination with other treatments for erectile dysfunction have not explored is the use of these combinations are not recommended.