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The pressure of other drugs on the metabolism of sildenafil. Sildenafil metabolism occurs mainly in the liver almost by the action of isoenzymes CYP3A4 (main pathway) and CYP2C9, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, respectively, increase the clearance of sildenafil.
With the simultaneous use of CYP3A4 inhibitors (ketoconazole, erythromycin, cimetidine), a decrease in the clearance of sildenafil was noted. Cimetidine (at a dose of 800 mg), which is a non-specific inhibitor of CYP3A4, the presence of simultaneous administration with sildenafil (at a dose of 50 mg) causes an increase in plasma concentration of essay by 56%.
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A single dose of sildenafil at a dose of 100 mg at once with erythromycin, a moderate inhibitor of CYP3A4 (correspondingly 500 mg 2 times / day per course of 5 days), against the background of reaching a constant concentration of erythromycin in the blood leads to an increase in the AUC of sildenafil by 182%. The presence of the simultaneous use of sildenafil (once at a dose of 100 mg) and saquinavir (at a dose of 1200 mg 3 times / day), which is supposedly an inhibitor of HIV protease, for no reason and an inhibitor of CYP3A4, in order to achieve a constant concentration of saquinavir in the blood, C max of sildenafil in the blood increased for 140%, and AUC increased by 210%. Sildenafil has no effect on the pharmacokinetic parameters of saquinavir.
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Stronger inhibitors of the CYP3A4 isoenzyme, such as ketoconazole and itraconazole, may cause more pronounced changes in the pharmacokinetics of sildenafil. The simultaneous use of sildenafil (single dose of 100 mg) and ritonavir (500 mg 2 times / day), which is an inhibitor of HIV protease and a strong inhibitor of isoenzymes of the cytochrome P450 system, against the background of reaching a constant concentration of ritonavir in the blood leads to an increase in the C max of sildenafil for 300% (4 times), and AUC for 1000% (11 times). As a result of 24 hours, the concentration of sildenafil in the blood plasma was about 200 ng / ml (about a single use of one sildenafil - 5 ng / ml).