Clinical Pharmacokinetics

, Volume 47, Issue 9, pp 611–618

A Clinical Comparison of Slow- and Rapid-Escalation Treprostinil Dosing Regimens in Patients with Pulmonary Hypertension

  • Nika Skoro-Sajer
  • Irene M. Lang
  • Evis Harja
  • Meinhard P. Kneussl
  • Wendy Gin Sing
  • Simon J. R. Gibbs
Original Research Article

DOI: 10.2165/00003088-200847090-00004

Cite this article as:
Skoro-Sajer, N., Lang, I.M., Harja, E. et al. Clin Pharmacokinet (2008) 47: 611. doi:10.2165/00003088-200847090-00004

Abstract

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 slowescalation 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.

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Nika Skoro-Sajer
    • 1
  • Irene M. Lang
    • 1
  • Evis Harja
    • 1
  • Meinhard P. Kneussl
    • 2
  • Wendy Gin Sing
    • 3
  • Simon J. R. Gibbs
    • 3
  1. 1.Department of Internal Medicine II, Division of Cardiology, Vienna General HospitalMedical University of ViennaViennaAustria
  2. 2.Wilheminenspital der Stadt WienViennaAustria
  3. 3.National Heart & Lung Institute, Imperial College of ScienceTechnology & Medicine and Hammersmith HospitalLondonUK
  4. 4.Department of Internal Medicine II, Division of CardiologyMedical University of ViennaViennaAustria