Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial

Abstract

Background: 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).. Methods: 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 min until 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 2 /FiO 2) 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. Results: 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 2 /FiO 2 were significantly improved (P<0.05). Conclusions: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02865733.