Laboratory of Pharmacology, National Institute of Pediatrics, Avenida Imán N° 1, 3rd piso Colonia Cuicuilco, CP 04530, Mexico City, Mexico.
Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
World J Pediatr. 2017 Dec;13(6):588-592. doi: 10.1007/s12519-017-0043-4. Epub 2017 Aug 8.
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.
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.
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.
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.
最近，西地那非被引入用于治疗肺动脉高压（PAH）；然而，目前关于儿童西地那非药代动力学的研究较少。因此，我们旨在使用单剂量对患有 PAH 的儿童进行西地那非的药代动力学研究。
在获得父母或监护人的书面同意后，我们招募了 12 名被诊断为 PAH 的儿童（其中男性 10 名，女性 2 名）参与研究。使用我们实验室开发的临时儿科制剂，在口服 1mg/kg 西地那非后 0.25、0.5、1、2、4、8 和 12 小时采集血样。使用之前经过验证的高效液相色谱法对样本进行分析。
使用考虑到 Akaike 信息准则（AIC）以选择更可调节模型的 WinNonlin 3.1 程序进行药代动力学分析。得到以下药代动力学参数：最大浓度（C）：366±179ng/mL，最大浓度时间（Tmax）：0.92±0.30 小时，消除半衰期（t）：2.41±1.18 小时，总清除率（CL/F）：5.85±2.81 L/小时，分布容积（Vd/F）：20.13±14.5 L，吸收速率常数（Ka）：0.343 小时，消除速率（Ke）：0.35 小时，从 0 到无穷大的曲线下面积（AUC）：2061±618ng/mL/hour。使用 AIC 证实了所有患者数据均符合单室模型的调整。
Ka、Ke 和 t 参数与成人报道的参数相似；然而，C 和 Vd/F 值明显更高。基于这些发现，我们建议调整患有 PAH 的儿童的西地那非治疗方案。
