The influence of other drugs on the pharmacokinetics of sildenafil
Metabolism Sildenafil is mainly under the influence of cytochrome CYP3A4 (major route) and CYP2C9, so inhibitors of these isoenzymes may reduce sildenafil clearance and inducers, respectively, to increase the clearance of sildenafil. Decreased clearance of sildenafil, while the use of inhibitors of cytochrome CYP3A4 (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), nonspecific inhibitor isoenzyme Viagra online pharmacy cytochrome CYP3A4, when co-administered with sildenafil (50 mg) sildenafil causes an increase in the plasma concentration of 56%. A single dose of 100 mg sildenafil together with erythromycin (500 mg / day, 2 times a day for 5 days), a specific inhibitor of the isoenzyme cytochrome CYP3A4, against the backdrop of a constant concentration of erythromycin in the blood leads to an increase in AUC of sildenafil at 182%.
When co-administered sildenafil (100 mg single dose) and saquinavir (1200 mg / day, 3 times a day), an inhibitor of HIV protease and isoenzyme cytochrome CYP3A4, against the backdrop of a constant concentration in the blood saquinavir sildenafil Cmax increased by 140%, a AUC was increased by 210%. Sildenafil has no effect on the pharmacokinetics of saquinavir.
More potent inhibitors isoenzyme cytochrome CYP3A4, such as itraconazole and ketoconazole, and may cause larger changes of sildenafil pharmacokinetics.
Effect of Sildenafil on other drugs
Simultaneous use of sildenafil (100 mg single dose) and ritonavir (500 mg, 2 times a day), HIV protease inhibitor and a potent inhibitor of cytochrome P450, against the backdrop of a constant concentration of ritonavir in the blood leads to an increase in Cmax of sildenafil 300% (4 times ), a AUC 1000% (11 times). After 24 hours the concentration of sildenafil in plasma is about 200 ng / ml (after a single application of sildenafil - 5 ng / ml), which agrees with the information about the pronounced effect of ritonavir on the pharmacokinetics of various substrates cytochrome P450 Generic Viagra online . Sildenafil has no effect on the pharmacokinetics of ritonavir. Concomitant use of sildenafil with ritonavir is not recommended. If sildenafil is taken at the recommended doses, patients receiving both potent inhibitors isoenzyme cytochrome CYP3A4, the sildenafil free Cmax is less than 200 nM, and the drug was well tolerated.
A single dose of antacid (magnesium hydroxide / aluminum hydroxide) did not affect the bioavailability of sildenafil.
Inhibitors of cytochrome CYP2C9 (tolbutamide, warfarin), cytochrome CYP2D6 (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide diuretics, ACE inhibitors and calcium antagonists have no effect on the pharmacokinetics of sildenafil.
Azithromycin (500 mg / day for 3 days) did not affect the AUC, Cmax Tmax, elimination rate constant and T1 / 2 of sildenafil or a main circulating metabolite.
Effect of Sildenafil on other drugs
Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes -1A2, 2C9, 2C19, 2D6, 2E1 and ZA4 (IC50> 150 mM). When taken at the recommended doses of sildenafil Cmax it is about 1 mol, it is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.
Sildenafil enhances the hypotensive effect of nitrates as a long-term use of the latter, and upon appointment of acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donators contraindicated.
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