Pharmacokinetics and Steady-State Bioequivalence of Treprostinil Sodium (Remodulin®) Administered by the Intravenous and Subcutaneous Route to Normal Volunteers

Laliberte, Kevin; Arneson, Carl; Jeffs, Roger; Hunt, Thomas L.; Wade, Michael S.

doi:10.1097/00005344-200408000-00010

Cited by 166 publications

(128 citation statements)

References 5 publications

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“…However, the structural remodelling could not be strongly reversed by treprostinil treatment in the hypoxic chimeric mice with the applied infusion rate of 14 ng?kg -1 ?min -1 . This rate of infusion has been shown to exert strong effects on human pulmonary haemodynamics and is approximately the starting dose for patients [26][27][28][29]. Patients on chronic treprostinil infusion treatment may need increased doses, up to 60 ng?kg -1 ?min -1 .…”

Section: Discussionmentioning

confidence: 99%

Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension

Nikam

Schermuly²,

Dumitrascu³

et al. 2010

European Respiratory Journal

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A unique subpopulation of peripheral blood mononuclear cells that exhibit a parallel expression of haematopoietic and mesenchymal markers has been described as ''circulating fibrocytes''. These cells were demonstrated to obtain a fibroblastic phenotype in tissues or cell culture and contribute to pulmonary fibrotic disorders and tissue remodelling processes.The aim of our study was to characterise the recruitment of circulating fibrocytes in vivo in the model of chronic hypoxic pulmonary hypertension in mice and to analyse the therapeutic effect of the stable prostacyclin analogue trepostinil with respect to this cell population.To track circulating fibrocytes in vivo, we transplanted wild-type mice with bone marrow from ubiquitously eGFP expressing mice and subjected them to chronic hypoxia. We observed significantly increased recruitment of circulating fibrocytes to the remodelled pulmonary resistance arteries in response to hypoxia. Treatment with treprostinil significantly reduced the recruitment of these cells compared to normoxic mice. Treprostinil also reduced right ventricular systolic pressure and slightly reduced the vascular remodelling but failed to reverse the right ventricular hypertrophy.In summary, we show that circulating fibrocytes contribute to hypoxic pulmonary vascular remodelling and may be specifically targeted by a prostacyclin analogue. Further investigations of cellular and paracrine mechanisms are warranted to decipher their role in pulmonary hypertension.

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Section: Discussionmentioning

confidence: 99%

Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension

Nikam

Schermuly²,

Dumitrascu³

et al. 2010

European Respiratory Journal

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“…Iloprost treatment provided clinical efficacy by intravenous [3] and inhaled application [5]. Treprostinil has a significantly extended half life [6]. It is approved for i.v.…”

Section: Introductionmentioning

confidence: 99%

Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension

Voswinckel

Reichenberger

Gall

et al. 2009

Pulmonary Pharmacology & Therapeutics

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“…or s.c. administration [34] or inhalation [35]. Several studies that included both older children and adults demonstrated or suggested efficacy of treprostinil i.v.…”

Section: Treprostinilmentioning

confidence: 99%

Treatment options for paediatric pulmonary arterial hypertension

Berger¹,

Bonnet²

2010

European Respiratory Review

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Pulmonary arterial hypertension (PAH) is a serious, progressive condition, which can present idiopathically or secondary to conditions such as systemic sclerosis or congenital heart disease. The condition exists in both adult and paediatric forms, which possess several similar characteristics. Adult and paediatric PAH can, however, be distinguished based on underlying pathology and the presence of age-specific conditions, some of which are related to poor lung development in children. Improved knowledge of vascular biology has led to the development of several PAH-specific therapies, which have demonstrated clinical benefits in adults, including improved exercise capacity and prolonged survival. Treatment data in paediatric PAH are scarce. Although limited, the existing data indicate that current treatments for paediatric PAH are well tolerated and effective, at least in the short-and medium-term. Nevertheless, the current guidelines for clinicians, which recommend use of the adult treatment algorithm in paediatric patients, appear justified when judged according to the available evidence. However, further randomised, controlled trials are necessary to increase the evidence base for treatment of paediatric PAH, especially in relation to age-specific conditions. At present, early initiation of treatment and combination pharmacological therapy may offer the most promising courses of action to improve outcomes in paediatric PAH.

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Pharmacokinetics and Steady-State Bioequivalence of Treprostinil Sodium (Remodulin®) Administered by the Intravenous and Subcutaneous Route to Normal Volunteers

Cited by 166 publications

References 5 publications

Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension

Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension

Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension

Treatment options for paediatric pulmonary arterial hypertension

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