Pharmacokinetics and steady-state bioequivalence of treprostinil sodium (Remodulin) administered by the intravenous and subcutaneous route to normal volunteers

J Cardiovasc Pharmacol. 2004 Aug;44(2):209-14. doi: 10.1097/00005344-200408000-00010.

Abstract

Treprostinil sodium is a chemically stable analogue of prostacyclin administered as a chronic, continuous subcutaneous infusion for the treatment of pulmonary arterial hypertension (PAH). There has been significant clinical interest in determining the feasibility of delivering treprostinil by intravenous infusion. Therefore, a bioequivalence and comparative pharmacokinetics study of the two routes of administration was conducted in normal volunteers. A randomized, two-period, crossover study design was employed. Each subject was dosed at 10 ng/kg/min for 72 hours by each route, with the infusions separated by a 4-day wash-out period. In the 51 subjects who received at least 24 hours of treprostinil administered subcutaneously and intravenously, the steady-state ratios of the geometric means (i.v./s.c.) and 90% confidence intervals for AUCss and Cmaxss were 92.9% (89.8-96.1%) and 106% (99.4-113%), respectively. Secondary pharmacokinetic assessments confirmed the comparability of the two routes of administration at steady state, and also demonstrated that the elimination half-life of treprostinil was 4.4 and 4.6 hours following intravenous and subcutaneous administration, respectively. Based on these findings it was concluded that intravenously and subcutaneously administered treprostinil are bioequivalent at steady state.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Area Under Curve
  • Cross-Over Studies
  • Drug Administration Schedule
  • Epoprostenol / administration & dosage
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / blood
  • Epoprostenol / pharmacokinetics*
  • Female
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Male
  • Metabolic Clearance Rate / drug effects
  • Metabolic Clearance Rate / physiology
  • Middle Aged
  • Therapeutic Equivalency
  • Time Factors

Substances

  • Epoprostenol
  • treprostinil