Sildenafil is a competitive and selective inhibitor of phosphodiesterase 5. Sildenafil is cleared by hepatic CYP3A (major route) and CYP2C9 (minor route) and concomitant administration of potent CYP3A inducers (e.g., bosentan) causes decreases in plasma levels of sildenafil. CYP3A4 inhibitors (erythromycin and cimetidine) inhibit sildenafil metabolism prolonging the half-life and elevating blood levels of sildenafil. Sildenafil is a pulmonary arterial vasodilator and it has been used in the treatment of persistent pulmonary hypertension. The initial oral dose is 250 to 500 µg/kg 4 times-daily in infants and the oral dose is 10 to 20 mg thrice-daily in children with a body-weight up to 20 kg or > 20 kg, respectively. Sildenafil has been found efficacy and safe in infants and children but it may induce adverse-effects. Following an oral dosing, the absorption rate constant is 0.343 h-1, and the elimination half-life is 2.41 hours in children suggesting that sildenafil is rapidly absorbed and eliminated. The interaction of sildenafil with drugs and the metabolism of sildenafil have been extensively studied. The principal routes of sildenafil metabolism are: N-demethylation, oxidation, and aliphatic dihydroxylation, and the major metabolite is N-desmethyl sildenafil. The treatment of infants and children with sildenafil has been extensively studied. Sildenafil citrate and sildenafil cross the human placenta and sildenafil migrates into the breast-milk in significant amounts. The aim of this study is to review the sildenafil dosing, efficacy and safety, effects, adverse-effects, pharmacokinetics, interaction with drugs, metabolism, treatments, and sildenafil placental transfer and migration into the breast-milk.
CYP2A6 Genotype but not Age Determines Cotinine Half-Life in Infants and Children
