The effect of other drugs
Metabolism of sildenafil occurs mainly in the liver under the influence of isoenzymes CYP3A4 (major route) and CYP2C9, therefore, inhibitors of these isoenzymes may reduce the clearance of sildenafil and inductors, respectively, to increase the clearance of sildenafil.
Use of inhibitors of CYP3A4
Cimetidine (at dose 800 mg), which is a nonspecific inhibitor of CYP3A4, together with the admission of sildenafil (the dose of 50 mg) is increasing the concentration of sildenafil in plasma is 56%. Sildenafil is a weak inhibitor of isoenzymes of cytochrome P450 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4.
A single dose of sildenafil
A dose of 100 mg simultaneously with erythromycin - specific inhibitor of CYP3A4 (erythromycin 500 mg 2 times/day for 5 days) - against the backdrop of achieving constant concentration of erythromycin in the blood leads to an increase in AUC of sildenafil at 182%.
Simultaneous use of sildenafil
Sildenafil is both an inhibitor of HIV protease, and inhibitor of CYP3A4, on the background of sustained concentrations of saquinavir in the blood, a Cmax of sildenafil in the blood was increased by 140%, and AUC was increased by 210%. Sildenafil had no effect on the pharmacokinetic parameters of saquinavir.
Strong inhibitors of CYP3A4
Concomitant use of sildenafil (single dose of 100 mg) and ritonavir (500 mg 2 times/day), an inhibitor of HIV protease and a strong inhibitor of isoenzymes of cytochrome P450, amid achieve a constant concentration of ritonavir in the blood leads to an increase in Cmax of sildenafil by 300%
Taken in the recommended doses
Patients receiving concomitant strong CYP3A4 inhibitors, Cmax free sildenafil does not exceed 200 nm, and the drug was well tolerated. A single dose of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil.