Comparative bioavailability of inhaled treprostinil administered as LIQ861 and Tyvaso® in healthy subjects

Vascul Pharmacol. 2021 Jun;138:106840. doi: 10.1016/j.vph.2021.106840. Epub 2021 Feb 2.

Abstract

Introduction: Treprostinil is a synthetic prostacyclin analogue approved for inhalation administration to patients with pulmonary arterial hypertension (PAH) via nebulized Tyvaso® inhalation solution. LIQ861 is an inhaled, dry-powder formulation of treprostinil produced using Print® (Particle Replication in Nonwetting Templates) technology, a proprietary process for designing and producing highly uniform drug particles.

Methods: We conducted comparative bioavailability analyses of treprostinil exposure from LIQ861 (79.5 μg capsule [approximate delivered dose of 58.1 μg treprostinil]) compared with Tyvaso® (9 breaths [approximate delivered dose of 54 μg treprostinil]).

Results: Treprostinil exposure parameters had least squares geometric mean ratios (LIQ861: Tyvaso®) between 0.9 and 1.0 with 90% confidence intervals contained within 0.8 to 1.25. LIQ861 and Tyvaso® were both well tolerated.

Discussion: Results showed comparable bioavailability of treprostinil and similar tolerability for LIQ861 and Tyvaso® administered to healthy adults.

Conclusions: Given the comparable treprostinil bioavailability and similar safety profiles of LIQ861 and Tyvaso®, LIQ861 fulfills a significant unmet need for PAH patients by maximizing the therapeutic benefits of treprostinil by safely delivering doses to the lungs in 1 to 2 breaths using a discreet, convenient, easy-to-use inhaler.

Keywords: Bioavailability; Inhaled treprostinil; Pharmacokinetic; Pulmonary arterial hypertension.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / pharmacokinetics*
  • Biological Availability
  • Drug Compounding
  • Dry Powder Inhalers
  • Epoprostenol / administration & dosage
  • Epoprostenol / adverse effects
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacokinetics
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Powders
  • Pulmonary Arterial Hypertension / drug therapy*
  • Pulmonary Arterial Hypertension / physiopathology
  • Young Adult

Substances

  • Antihypertensive Agents
  • Powders
  • Epoprostenol
  • treprostinil