A clinical comparison of slow- and rapid-escalation treprostinil dosing regimens in patients with pulmonary hypertension

Clin Pharmacokinet. 2008;47(9):611-8. doi: 10.2165/00003088-200847090-00004.


Background and objective: Subcutaneous treprostinil is an effective treatment for pulmonary arterial hypertension (PAH). A previous pivotal study indicated that infusion site pain was dose dependent and resulted in suboptimal dose escalation by week 12 and a reduced clinical benefit. We hypothesized that a rapid-escalation treprostinil dosing regimen would be as safe and effective as a slow-escalation dosing regimen.

Methods: Twenty-three patients received treprostinil to treat PH of various aetiologies and were randomized into two groups. Group 1 (11 patients: seven females and four males, aged 51.7 +/- 15.4 years) received a slow-escalation regimen, and group 2 (12 patients: ten females and two males, aged 51.3 +/- 16.7 years) were exposed to rapid dose escalation. The dose escalation, exercise capacity (a 6-minute walk test [6WT] or a shuttle walk test [SWT]), WHO classification, blood pressure, heart rate, respiration rate, baseline haemodynamics and adverse events were followed up for 12 weeks.

Results: Baseline haemodynamics did not differ significantly between the treatment groups. At follow-up, the treprostinil dose reached 12.9 +/- 2.7 ng/kg/min in group 1 and 20.3 +/- 5.8 ng/kg/min in group 2 (p < 0.01). The patients' WHO classification improved significantly (p < 0.05), with no difference between the groups. Improvement of exercise capacity was greater in group 2 (6WT and SWT, p < 0.05). Infusion site pain occurred in 81.8% of group 1 and in 58.3% of group 2 (p < 0.05) patients. Other adverse events and changes in the heart rate, respiration rate and blood pressure were similar in both groups.

Conclusion: The rapid-dosing regimen is as safe and effective as the slow-escalation regimen and may be associated with even better clinical outcomes. Infusion site pain is not dose dependent.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epoprostenol / administration & dosage
  • Epoprostenol / adverse effects
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / therapeutic use
  • Exercise Tolerance
  • Female
  • Follow-Up Studies
  • Heart Rate
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Infusions, Subcutaneous
  • Male
  • Middle Aged
  • Respiration / drug effects
  • Young Adult


  • Antihypertensive Agents
  • Epoprostenol
  • treprostinil