Oral treprostinil diethanolamine for pulmonary arterial hypertension

Feldman, Jeremy; Im, Yunhee; Gill, Kirat

doi:10.1586/17512433.2015.984690

Cited by 5 publications

(2 citation statements)

References 8 publications

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“…Orenitram™ is treprostinil in an extended-release tablet formulation for the treatment of patients with pulmonary arterial hypertension. 68 The approval comes after the FREEDOM studies. 69,70 Whilst current data in patients not previously taking prostacyclin drugs are disappointing, studies show that in some patients oral treprostinil may successfully replace existing use of continuously infused drug.…”

Section: Limitations Of Prostacyclin Drugs In Pulmonary Arterial Hypementioning

confidence: 99%

Role of prostacyclin in pulmonary hypertension

Mitchell¹,

Ahmetaj‐Shala²,

Kirkby³

et al. 2014

Global Cardiology Science and Practice

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Prostacyclin is a powerful cardioprotective hormone released by the endothelium of all blood vessels. Prostacyclin exists in equilibrium with other vasoactive hormones and a disturbance in the balance of these factors leads to cardiovascular disease including pulmonary arterial hypertension. Since it's discovery in the 1970s concerted efforts have been made to make the best therapeutic utility of prostacyclin, particularly in the treatment of pulmonary arterial hypertension. This has centred on working out the detailed pharmacology of prostacyclin and then synthesising new molecules based on its structure that are more stable or more easily tolerated. In addition, newer molecules have been developed that are not analogues of prostacyclin but that target the receptors that prostacyclin activates. Prostacyclin and related drugs have without doubt revolutionised the treatment and management of pulmonary arterial hypertension but are seriously limited by side effects within the systemic circulation. With the dawn of nanomedicine and targeted drug or stem cell delivery systems it will, in the very near future, be possible to make new formulations of prostacyclin that can evade the systemic circulation allowing for safe delivery to the pulmonary vessels. In this way, the full therapeutic potential of prostacyclin can be realised opening the possibility that pulmonary arterial hypertension will become, if not curable, a chronic manageable disease that is no longer fatal. This review discusses these and other issues relating to prostacyclin and its use in pulmonary arterial hypertension.

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Section: Limitations Of Prostacyclin Drugs In Pulmonary Arterial Hypementioning

confidence: 99%

Role of prostacyclin in pulmonary hypertension

Mitchell¹,

Ahmetaj‐Shala²,

Kirkby³

et al. 2014

Global Cardiology Science and Practice

View full text Add to dashboard Cite

show abstract

“…Remodulin administration is associated with significant injection site pain (s.c.) or concern of infection (i.v. administration) (Simonneau et al, 2002;Remodulin, 2014); however, Orenitram and Tyvaso require multiple doses daily, and efficacy may not be fully maintained over a 24-hour period (Channick et al, 2012;Tyvaso, 2013;Orenitram, 2014;Feldman et al, 2015). Inhaled TRE is also associated with numerous adverse side effects, which limits the dose.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Pharmacology and Pharmacokinetics of Inhaled Hexadecyl-Treprostinil (C16TR), a Pulmonary Vasodilator Prodrug

Corboz

Malinin

et al. 2017

J Pharmacol Exp Ther

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This article describes the preclinical pharmacology and pharmacokinetics (PK) of hexadecyl-treprostinil (C16TR), a prodrug of treprostinil (TRE), formulated in a lipid nanoparticle (LNP) for inhalation as a pulmonary vasodilator. C16TR showed no activity (>10 M) in receptor binding and enzyme inhibition assays, including binding to prostaglandin E receptor 2, prostaglandin D receptor 1, prostaglandin I receptor, and prostaglandin E receptor 4; TRE potently bound to each of these prostanoid receptors. C16TR had no effect (up to 200 nM) on platelet aggregation induced by ADP in rat blood. In hypoxia-challenged rats, inhaled C16TR-LNP produced dose-dependent (0.06-6 g/kg), sustained pulmonary vasodilation over 3 hours; inhaled TRE (6g/kg) was active at earlier times but lost its effect by 3 hours. Single- and multiple-dose PK studies of inhaled C16TR-LNP in rats showed proportionate dose-dependent increases in TRE and area under the curve (AUC) for both plasma and lung; similar results were observed for dog plasma levels in single-dose PK studies. In both species, inhaled C16TR-LNP yielded prolonged plasma TRE levels and a lower plasma TRE compared with inhaled TRE. Inhaled C16TR-LNP was well tolerated in rats and dogs; TRE-related side effects included cough, respiratory tract irritation, and emesis and were seen only after high inhaled doses of C16TR-LNP in dogs. In guinea pigs, inhaled TRE (30 g/ml) consistently produced cough, but C16TR-LNP (30g/ml) elicited no effect. These results demonstrate that C16TR-LNP provides long-acting pulmonary vasodilation, is well tolerated in animal studies, and may necessitate less frequent dosing than inhaled TRE with possibly fewer side effects.

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Corticotrophins, Corticosteroids, and Prostaglandins

Brophy

Ray

2016

Side Effects of Drugs Annual

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Oral treprostinil diethanolamine for pulmonary arterial hypertension

Cited by 5 publications

References 8 publications

Role of prostacyclin in pulmonary hypertension

Role of prostacyclin in pulmonary hypertension

Preclinical Pharmacology and Pharmacokinetics of Inhaled Hexadecyl-Treprostinil (C16TR), a Pulmonary Vasodilator Prodrug

Corticotrophins, Corticosteroids, and Prostaglandins

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