Original ArticleSubcutaneous and Intravenous Treprostinil Pharmacokinetics in Children With Pulmonary Vascular DiseaseHall, Keeley BS*; Ogawa, Michelle PNP*; Sakarovitch, Charlotte MS†; Hopper, Rachel K. MD*; Adamson, Gregory T. MD*; Hanna, Brian MD‡; Ivy, David D. MD§; Miller-Reed, Kathleen PNP§; Yung, Delphine MD¶; McCarthy, Elisa BS*; Siehr-Handler, Stephanie L. MD║; Feinstein, Jeffrey A. MD*,**Author Information *Department of Pediatrics (Cardiology), Lucile Packard Children's Hospital Stanford, Stanford University, Palo Alto, CA; †Quantitative Sciences Unit, Division of Biomedical Informatics Research, Department of Medicine, Stanford University, Palo Alto, CA; ‡Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, PA; §Department of Pediatrics, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, CO; ¶Department of Cardiology, Seattle Children's Hospital, Seattle, WA; ║Department of Pediatrics (Cardiology), Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WA; and **Department of BioEngineering, Stanford University, Palo Alto, CA. Reprints: Jeffrey A. Feinstein, MD, Division of Pediatric Cardiology, Department of Bioengineering, Stanford University School of Medicine, 750 Welch Road–Suite 305, Palo Alto, CA 94304 (e-mail: [email protected]). This study was funded by United Therapeutics; J. A. Feinstein, R. K. Hopper, D. D. Ivy, and S. L. Siehr-Handler have additional recent or ongoing research funded by United Therapeutics. This study was supported by the Vera Moulton Wall Center for Pulmonary Vascular Disease at Stanford. The authors report no conflicts of interest. Journal of Cardiovascular Pharmacology: June 2019 - Volume 73 - Issue 6 - p 383-393 doi: 10.1097/FJC.0000000000000674 Buy Metrics Abstract This study evaluated the pharmacokinetics of intravenous (IV) and subcutaneous (SC) treprostinil in pediatric patients with pulmonary vascular disease, and compared them with existing adult data from a similar cohort. Blood samples were collected from pediatric patients receiving steady-state IV or SC treprostinil and were assessed for plasma treprostinil concentration using liquid chromatography and tandem mass spectrometry. Forty participants, 15 receiving IV and 25 receiving SC treprostinil, were included in the analysis. Age ranged from 0.1 to 15.6 years. The median dose of treprostinil was 45.5 ng·kg−1·min−1 with a range of 8–146 ng·kg−1·min−1. There was a linear relationship between treprostinil dose and plasma concentration with an R2 of 0.57. On average, there were higher blood concentrations per given dose of IV treprostinil compared with those per given dose of SC, but the difference was not significant. Compared with adult data, the slope of the pediatric data was similar, but the y-intercept was significantly lower. Additionally, the concentration per dose ratio was significantly higher in adults compared with children. Pediatric patients have significantly lower average blood concentrations of treprostinil per given dose compared with adults, and higher, but not significantly so, blood concentrations when treprostinil is administered IV as compared with SC administration. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.