Pharmacokinetics of oral treprostinil sustained release tablets during chronic administration to patients with pulmonary arterial hypertension

R. James White, Fernando Torres, Roblee Allen, Carlos Jerjes, Tomas Pulido, David Yehle, Meredith Howell, Kevin Laliberte, Jean Francois Marier, Victor F. Tapson

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Pulmonary arterial hypertension (PAH) is a progressive vascular disease that ultimately leads to right ventricular failure and death. Treprostinil diolamine is an oral prostacyclin analogue; sustained release tablets of oral treprostinil are currently being evaluated for efficacy and safety as a potential therapy in patients with PAH. Previous attempts at developing an oral prostanoid have been limited by rapid absorption and short plasma half-life; thus, the aim of this study was to characterize the pharmacokinetic profile of treprostinil diolamine in PAH patients after chronic dosing. The study enrolled 74 PAH patients who had been taking treprostinil diolamine for a minimum of 4 weeks (range: 0.5-16 mg). We collected plasma samples over 12 hours and estimated pharmacokinetic parameters using noncompartmental methods. Seventy patients had complete data. After chronic twice-daily oral dosing of treprostinil diolamine, mean area under the curve (AUC0-12) of treprostinil increased from 5244 to 20,4086 pg·hr-1- ·mL-1 and mean maximum observed plasma concentration (C max) increased from 1383 to 33588 pg/mL. The apparent clearance (CL/F) was similar across all doses, indicating a linear dose-exposure relationship after twice-daily dosing. We conclude that twice-daily oral treprostinil provides sustained and proportional treprostinil concentrations over a wide range of doses during chronic administration to PAH patients.

Original languageEnglish (US)
Pages (from-to)474-481
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume61
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • Pharmacokinetics
  • Prostacyclin
  • Pulmonary hypertension
  • Treprostinil

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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