Faculty Collaboration Database

Pharmacokinetics of Oral Treprostinil in Children With Pulmonary Arterial Hypertension. J Cardiovasc Pharmacol 2020 Jul;76(1):94-100

Date

05/14/2020

Pubmed ID

32398473

DOI

10.1097/FJC.0000000000000842

Scopus ID

2-s2.0-85088209247 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

As part of a clinical trial, this study examined the pharmacokinetics (PK) of oral treprostinil (TRE) in children with pulmonary arterial hypertension. The trial consisted of the following 3 cohorts: transition from parenteral (cohort 1) or inhaled (cohort 2) TRE, or de novo addition (cohort 3). Oral TRE was dosed 3 times daily. PK samples were obtained before an oral TRE dose, and at 2, 4, 6, and 8 hours thereafter. The PK parameters were calculated using noncompartmental analysis. Thirty-two children (n = 10 in cohorts 1 and 2, n = 12 in cohort 3) were enrolled; the median age was 12 years (range 7-17 years), and the median weight was 42.2 kg (range 19.3-78 kg). The median oral TRE dose for all subjects was 3.8 mg (5.9, 3.5, and 4.0 mg for cohorts 1, 2, and 3, respectively). The TRE concentration versus time profile demonstrated a peak concentration at a median of 3.8 hours with wide variability. In cohort 1, oral dosing led to higher peak (5.9 ng/mL) and lower trough (1 ng/mL) concentrations than parenteral (peak 5.4 ng/mL and trough 4.2 ng/mL), but a lower mean concentration (3.61 vs. 4.46 ng/mL), likely due to variable metabolism and noncomparable dosing. Both the area under the curve and average concentration were linearly correlated with oral TRE dose and dose normalized to body weight, but not with weight or age alone. In pediatric patients, an increased oral TRE dose or dose frequency may be required to minimize PK variability and achieve greater correlation with parenteral dosing.

Author List

Hopper RK, Ivy DD, Yung D, Mullen MP, Hanna BD, Kirkpatrick E, Hirsch R, Austin ED, Fineman J, Solum D, Deng CQ, Feinstein JA

Author

Edward C. Kirkpatrick DO Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Adolescent
Age Factors
Antihypertensive Agents
Arterial Pressure
Child
Drug Administration Schedule
Epoprostenol
Female
Humans
Male
Models, Biological
Pulmonary Artery
Treatment Outcome
United States