تعیین شاخص های فارماکوکینتیکی شربت سیلدنافیل در هیپرتانسیون ریوی کودکان

Background and purpose: Pulmonary arterial hypertension (PAH) is a fatal disease affecting patients in all ages that could result in acute and chronic heart failure with high mortality rate. Oral sildenafil is approved to treat PAH in adults and recently in children. There are limited studies on the pharmacokinetics parameters of sildenafil, therefore, this study was designed to determine the pharmacokinetics properties of sildenafil syrup in pediatric pulmonary hypertension. Materials and methods: In this interventional open-label prospective study, 20 children aged between two months to 12 years with PAH were included. The patients received sildenafil syrup 0.5 mg/kg every 12 hour, which was increased to 2 mg/kg every 12 hour (if necessary) to control the pulmonary hypertension. Minimum treatment period was 12 weeks. A week after initiating therapy or dose change five plasma samples were obtained to determine the pharmacokinetic parameters of sildenafil. The samples were determined by HPLC and the data was analyzed using P-Pharm software. Results: Among the subjects, 17 including nine boys and eight girls completed the study. The mean of sildenafil dose was 1.6 mg/kg/day and the opened one-compartment was considered as the best pharmacokinetic model. The sildenafil pharmacokinetic parameters were Cl=4.19±1.35L/h, t1/2=4.94±1.49h and Vd=27.86±7.39L. The most prevalent side effect of the drug was hot flash. Conclusion: Pharmacokinetic parameters of sildenafil in children with pulmonary hypertension were similar to adults. The patients easily tolerated sildenafil syrup and no severe or serious side effect was observed. Therefore, sildenafil could be considered as a safe and cheap drug to manage pediatric pulmonary hypertension.