Pharmacokinetics of sildenafil in children with pulmonary arterial hypertension.

Background: Recently, sildenafil was introduced to treat pulmonary arterial hypertension (PAH); however, there are currently few studies on the pharmacokinetics of sildenalfil in children. Therefore, we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose.

Methods: Twelve children diagnosed with PAH, consisting of with ten males and two females, were recruited for the study after obtaining written consent from their parents or guardians. Blood samples were obtained predose and at 0.25, 0.5, 1, 2, 4, 8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory. The samples were analyzed using a previously validated high performance liquid chromatography method.

Results: A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for selecting a more adjustable model was performed. The following pharmacokinetic parameters were obtained: maximal concentration (C): 366±179 ng/mL, time to maximal concentration: 0.92±0.30 hours, elimination half-life (t): 2.41±1.18 hours, total clearance (CL/F): 5.85±2.81 L/hour, volume of distribution (Vd/F): 20.13±14.5 L, absorption rate constants (Ka): 0.343 hour, elimination rate (Ke): 0.35 hour, area under curve from zero to infinity: 2061±618 ng/mL/hour. The data of all patients adjusted to the model of one compartment were corroborated using AIC.

Conclusions: The parameters Ka, Ke and t were found to be similar to those reported in adults; however, the values of C and Vd/F were significantly higher. Based on these findings, we propose that treatment regimen of sildenafil be adjusted in children with PAH.