Population Pharmacokinetics of Sildenafil in Term Neonates: Evidence of Rapid Maturation of Metabolic Clearance in the Early Postnatal Period
作者： A Mukherjee , T Dombi , B Wittke , R Lalonde
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摘要: The phosphodiesterase 5 inhibitor sildenafil is a potential therapeutic option in the treatment of persistent pulmonary hypertension newborn (PPHN) and neonatal hypoxemia. In this open-label trial, 36 term neonates with PPHN or hypoxemia were administered intravenous for up to 7 days starting within 72 h birth. A mixed-effects pharmacokinetic model that included two-compartment disposition its metabolite an effect postnatal age on clearance was used describe plasma concentration-time data parent metabolite. Allometrically scaled increased threefold from first day after birth values similar those adults by week. Volume distribution fourfold higher than adults, resulting longer terminal half-life (48-56 h) compared adults. Increase early period likely reflects maturation CYP-mediated N-demethylation.
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