Authors: Skoro-Sajer, Nika¹; Lang, Irene M.¹; Harja, Evis¹; Kneussl, Meinhard P.²; Gin Sing, Wendy³; Gibbs, Simon J.R.³

Source: Clinical Pharmacokinetics, Volume 47, Number 9, 2008 , pp. 611-618(8)

Publisher: Adis International

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 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.

Keywords: Dose response; Prostaglandins; Pulmonary hypertension; Treprostinil

Document Type: Research article

Affiliations: 1: 1 Department of Internal Medicine II, Division of Cardiology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria 2: 2 Wilheminenspital der Stadt Wien, Vienna, Austria 3: 3 National Heart & Lung Institute, Imperial College of Science, Technology & Medicine and Hammersmith Hospital, London, UK

Publication date: 2008-01-01

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