Chen Xi, Cai Xiao-Man, Zhang Ming-Jie, Xu Jing-Han, Li Hao, Xu Zhuo-Ming
Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Pharmacy, Clinical Research Center, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ann Transl Med. 2021 Jul;9(14):1163. doi: 10.21037/atm-21-3188.
Application of Treprostinil (TRE) in the patients with single ventricle (SV) physiology is very limited, and the optimal dose for children has not been determined. In this study, we aimed to analyze plasma samples to assess the attainment of clinically therapeutic concentrations of TRE and its efficacy and safety in the treatment of pediatric functional SV pulmonary arterial hypertension (FSV-PAH)..
Pediatric patients with FSV-PAH were recruited in this study. IV TRE at an initial rate of 5 ng/kg/min was administered through the femoral vein with an increase in rate to 10 ng/kg/min every 30 minuntil the aiming dose of 80 ng/kg/min had been reached. The drug was gradually discontinued after 12 h of treatment at a stable dose. The mean postoperative pulmonary artery pressure (mPAP), pulmonary-to-systemic arterial pressure ratio (Pp/Ps), and the ratio between arterial oxygen partial pressure and inhaled oxygen concentration (PaO/FiO) were used to evaluate the efficacy of TRE treatment. A multiple linear regression model was used to explore the relevant factors associated with TRE blood concentration.
A total of eight patients were enrolled in the investigation, with an age range of 2.5-9.9 years. The median stable dose of TRE was 70 ng/kg/min with a range of 55-75 ng/kg/min. The median subliminal dose was 55 ng/kg/min with a range of 25-75 ng/kg/min. A linear relationship was established between the TRE dose and the plasma concentration. TRE blood concentrations were associated with dose and patient height. After TRE treatment, mPAP, Pp/Ps, and PaO/FiO were significantly improved (P<0.05).
A linear relationship was found between the blood concentration of TRE and its dose. IV TRE was an effective therapy without serious side effects in pediatric patients with FSV-PAH.
ClinicalTrials.gov Identifier: NCT02865733.
曲前列尼尔（TRE）在单心室（SV）生理状态患者中的应用非常有限，儿童的最佳剂量尚未确定。在本研究中，我们旨在分析血浆样本，以评估TRE临床治疗浓度的达到情况及其在治疗小儿功能性SV肺动脉高压（FSV-PAH）中的疗效和安全性。
本研究招募了患有FSV-PAH的儿科患者。通过股静脉以5 ng/kg/min的初始速率静脉注射TRE，每30分钟速率增加至10 ng/kg/min，直至达到80 ng/kg/min的目标剂量。在稳定剂量治疗12小时后逐渐停药。使用平均术后肺动脉压（mPAP）、肺循环与体循环动脉压比值（Pp/Ps）以及动脉血氧分压与吸入氧浓度之比（PaO/FiO）来评估TRE治疗的疗效。使用多元线性回归模型探索与TRE血药浓度相关的因素。
共有8名患者参与调查，年龄范围为2.5至9.9岁。TRE的中位稳定剂量为70 ng/kg/min，范围为55至75 ng/kg/min。中位阈下剂量为55 ng/kg/min，范围为25至75 ng/kg/min。TRE剂量与血浆浓度之间建立了线性关系。TRE血药浓度与剂量和患者身高相关。TRE治疗后，mPAP、Pp/Ps和PaO/FiO均显著改善（P<0.05）。
发现TRE血药浓度与其剂量之间存在线性关系。静脉注射TRE对小儿FSV-PAH患者是一种有效的治疗方法，且无严重副作用。
ClinicalTrials.gov标识符：NCT02865733。
