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Treprostinil

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https://www.readbyqxmd.com/read/29436381/subcutaneous-treprostinil-in-congenital-heart-disease-related-pulmonary-arterial-hypertension
#1
Nika Skoro-Sajer, Christian Gerges, Olga Hajnalka Balint, Dora Kohalmi, Monika Kaldararova, Iveta Simkova, Johannes Jakowitsch, Harald Gabriel, Helmut Baumgartner, Mario Gerges, Roela Sadushi-Kolici, David S Celermajer, Irene Marthe Lang
OBJECTIVE: To assess the efficacy and safety of subcutaneous treprostinil in adult patients with congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after 12 months of treatment. METHODS: Consecutive adult patients with CHD-PAH received subcutaneous treprostinil to maximum tolerated doses in an observational study. RESULTS: Advanced CHD-PAH patients with WHO class III or IV disease (n=32, age 40±10 years, 20 females) received treprostinil for suboptimal response to bosentan (n=12), WHO functional class IV disease (FC, n=7) or prior to bosentan approval (n=13)...
February 7, 2018: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29421665/inhaled-hexadecyl-treprostinil-provides-pulmonary-vasodilator-activity-at-significantly-lower-plasma-concentrations-than-infused-treprostinil
#2
Richard W Chapman, Zhili Li, Michel R Corboz, Helena Gauani, Adam J Plaunt, Donna M Konicek, Franziska G Leifer, Charles E Laurent, Han Yin, Dany Salvail, Chad Dziak, Walter R Perkins, Vladimir Malinin
INS1009 is a long acting pulmonary vasodilator prodrug of treprostinil (TRE) that is formulated in a lipid nanoparticle for inhaled delivery by nebulization. This study examined the ability of INS1009 to inhibit vasoconstriction in the pulmonary vasculature of rats and dogs and the extent to which local activity within the lung contributes to its activity. Rats received a single dose of INS1009 by nose-only inhalation or were given a continuous intravenous (i.v.) infusion of TRE, followed by an i.v. challenge of the thromboxane mimetic pulmonary vasoconstrictor U46619 and the increase in pulmonary arterial pressure (PAP) was measured...
February 5, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29408757/therapeutic-administration-of-inhaled-ins1009-a-treprostinil-prodrug-formulation-inhibits-bleomycin-induced-pulmonary-fibrosis-in-rats
#3
Michel R Corboz, Jimin Zhang, Daniel LaSala, Keith DiPetrillo, Zhili Li, Vladimir Malinin, Jeremy Brower, Philip J Kuehl, Ted E Barrett, Walter R Perkins, Richard W Chapman
Idiopathic pulmonary fibrosis is a progressive and lethal disease and while there are now two approved drugs (Esbriet® and Ofev®) additional effective treatments are still needed. Recently, prostacyclin analogs such as iloprost and treprostinil (TRE) have been shown to exert some protection against bleomycin-induced pulmonary fibrosis in mice when administered in a prophylactic regimen. In this study, we evaluated the effect of the inhaled treprostinil prodrug hexadecyl-treprostinil (C16TR) formulated in a lipid nanoparticle (INS1009) administered therapeutically in a fibrotic rat model...
February 1, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29348469/treprostinil-inhibits-proliferation-and-extracellular-matrix-deposition-by-fibroblasts-through-camp-activation
#4
Christopher Lambers, Michael Roth, Peter Jaksch, Gabriella Muraközy, Michael Tamm, Walter Klepetko, Bahil Ghanim, Feng Zhao
Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-β1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-ß1 and PDGF-induced fibroblast proliferation and ECM deposition was investigated. Human peripheral lung fibroblasts of seven IPF patients and five lung donors were stimulated by PDGF, or TGF-β1, or the combination...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310475/human-factors-and-usability-engineering-in-the-development-of-smt-101-for-the-treatment-of-pulmonary-arterial-hypertension
#5
Peter Noymer, Assaf Shaked, Kay Newell
BACKGROUND: SMT-101, a novel, proprietary, water-resistant wearable infusion pump prefilled with a preset dosage of treprostinil, was designed to address many of the administration-related shortcomings of existing parenteral therapy for pulmonary arterial hypertension (PAH). The objective of the human factors (HF) program was to demonstrate that the SMT-101 system is safe and effective when used by patients with PAH, their caregivers, or healthcare providers. METHODS: The HF program for SMT-101 consisted of 8 studies (148 participants): an ethnographic study, an online survey of patients with PAH, 4 formative studies, a study of the instructions for use (IFU), and a summative study for validation...
January 9, 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29275453/inhaled-treprostinil-in-pulmonary-hypertension-associated-with-lung-disease
#6
Mariana Faria-Urbina, Rudolf K F Oliveira, Manyoo Agarwal, Aaron B Waxman
PURPOSE: Pulmonary hypertension (PH) in the setting of parenchymal lung disease adversely affects quality of life and survival. However, PH-specific drugs may result in ventilation/perfusion imbalance and currently, there are no approved PH treatments for this patient population. In the present retrospective study, data from 22 patients with PH associated with lung disease treated with inhaled treprostinil (iTre) and followed up clinically for at least 3 months are presented. METHODS: PH was defined by resting right heart catheterization as a mean pulmonary artery pressure (mPAP) ≥ 35 mmHg, or mPAP ≥ 25 mmHg associated with pulmonary vascular resistance ≥ 4 Woods Units...
December 23, 2017: Lung
https://www.readbyqxmd.com/read/29199910/impact-of-four-times-daily-dosing-of-oral-treprostinil-on-tolerability-and-daily-dose-achieved-in-pulmonary-hypertension
#7
James C Coons, Cheryl Bunner, David C Ishizawar, Michael G Risbano, Belinda Rivera-Lebron, Michael A Mathier, Stephen Y Chan, Marc A Simon
Oral treprostinil (TRE) is a prostacylin that is approved for the treatment of patients with pulmonary arterial hypertension (PAH). Dosing is approved for two or three times daily (t.i.d.); however, adverse effects, including gastrointestinal-related symptoms, may limit the ability to reach optimal doses. We report our experience with a four times daily (q.i.d.) regimen of oral TRE for goal-directed therapy of PAH. We describe three patients that were transitioned from infusion or inhaled TRE to oral TRE with initial t...
January 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29195500/an-implantable-pump-lenus-pro%C3%A2-in-the-treatment-of-pulmonary-arterial-hypertension-with-intravenous-treprostinil
#8
Marcin Kurzyna, Katarzyna Małaczyńska-Rajpold, Andrzej Koteja, Agnieszka Pawlak, Łukasz Chrzanowski, Michał Furdal, Zbigniew Gąsior, Wojciech Jacheć, Bożena Sobkowicz, Justyna Norwa, Tatiana Mularek-Kubzdela, Adam Torbicki
BACKGROUND: Subcutaneous treprostinil is a prostacyclin analogue used to treat pulmonary arterial hypertension (PAH). Due to local pain it can cause a deterioration of heart related quality of life (HRQoL) or even abandonment of treatment. The aim of this paper was to assess the feasibility of treatment with intravenous treprostinil administered by means of the Lenus Pro® implantable pump. METHODS: This was a retrospective, multi-center study involving 12 patients (8 females) with PAH treated with a subcutaneous infusion of treprostinil with intolerable pain at the infusion site...
December 2, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29145311/pulmonary-hypertension-as-a-manifestation-of-mitochondrial-disease-a-case-report-and-review-of-the-literature
#9
Shan Xu, Xiaoling Xu, Jisong Zhang, Kejing Ying, Yuquan Shao, Ruifeng Zhang
BACKGROUND: Mitochondrial diseases are a group of multisystem heterogeneous diseases caused by pathologic dysfunction of the mitochondrial respiratory chain. A wide range of clinical expression has been described. However, pulmonary hypertension has rarely been described in association with mitochondrial disease until the past decade, and there is no currently recognized treatment for the pulmonary hypertension complicated with mitochondrial disorder. PATIENT CONCERNS: We reported the case of a 15-year-old boy who presented with shortness of breath and exercise limitation after a cold, and the diagnosis of pulmonary hypertension was confirmed by right heart catheter...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29076824/preliminary-results-from-a-nationwide-adult-cardiology-perspective-for-pulmonary-hypertension-registry-on-clinical-outcome-and-survival-in-pulmonary-hypertension-groups-simurg
#10
Cihangir Kaymaz, Bülent Mutlu, M Serdar Küçükoğlu, Barış Kaya, Bahri Akdeniz, Burçak Kılıçkıran Avcı, Enbiya Aksakal, Mehmet Akbulut, Zehra Atılgan Arıtürk, Sümeyye Güllülü, Gülten Aydoğdu Taçoy, Meral Kayıkçıoğlu, Sanem Nalbantgil, Cihan Örem, Hatice Betül Erer, Murat Yüce, Necip Ermiş, Omaç Tüfekçioğlu, Mesut Demir, Mehmet Birhan Yılmaz, Mehmet Güngör Kaya, Hakan Kültürsay, Zeki Öngen, Lale Tokgözoğlu
OBJECTIVE: The present study was designed to evaluate the characteristics of pulmonary hypertension (PH) and adult cardiology practice patterns for PH in our country. METHODS: We evaluated preliminary survey data of 1501 patients with PH (females, 69%; age, 44.8±5.45) from 20 adult cardiology centers (AdCCs). RESULTS: The average experience of AdCCs in diagnosing and treating patients with PH was 8.5±3.7 years. Pulmonary arterial hypertension (PAH) was the most frequent group (69%) followed by group 4 PH (19%), group 3 PH (8%), and combined pre- and post-capillary PH (4%)...
October 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29073911/successful-transition-from-treprostinil-to-selexipag-in-patient-with-severe-pulmonary-arterial-hypertension
#11
Asuka Furukawa, Yuichi Tamura, Hiroya Iwahori, Masato Goto, Narutaka Ohashi, Teruo Okabe, Akio Kawamura
BACKGROUND: In this report, we describe the first successful case of transition from subcutaneous administration of treprostinil to selexipag in a patient with severe pulmonary arterial hypertension (PAH), by evaluating hemodynamic changes and exercise tolerance. CASE PRESENTATION: A 38-year-old female with idiopathic PAH (IPAH) had received initial triple combination therapy (macitentan PO, tadalafil PO, and treprostinil SC) and achieved excellent improvement in hemodynamics...
October 26, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29071454/what-is-the-role-of-oral-prostacyclin-pathway-medications-in-pulmonary-arterial-hypertension-management
#12
REVIEW
Rama El Yafawi, Joel A Wirth
PURPOSE OF REVIEW: Prostacyclin pathway medications have been shown to be highly efficacious in the treatment of pulmonary arterial hypertension (PAH) through multiple prospective clinical trials and more than two decades of clinical experience. The strongest support for prostacyclin use in PAH management is with parenteral administration. Numerous risks and limitations of parenteral delivery systems as well as significant patient burdens restrict widespread parenteral use. Highly effective and tolerable oral prostacyclin preparations to manage PAH have long been sought...
October 25, 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/29036983/-research-progress-on-the-treatment-of-pulmonary-arterial-hypertension-with-treprostinil
#13
Q Wu, L Jia, Z C Jing
No abstract text is available yet for this article.
September 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29021475/successful-pulmonary-artery-embolization-for-the-management-of-hemoptysis-in-a-patient-with-eisenmenger-syndrome-caused-by-patent-ductus-arteriosus
#14
Naoki Tamada, Kazuhiko Nakayama, Yuto Shinkura, Ken-Ichi Yanaka, Naoto Katayama, Takuya Okada, Masato Yamaguchi, Kensuke Matsumoto, Hidekazu Tanaka, Toshiro Shinke, Noriaki Emoto, Ken-Ichi Hirata
The patient was a 19-year-old woman who was diagnosed with patent ductus arteriosus complicating Eisenmenger syndrome at a previous medical institution. She was referred to our hospital and arranged for lung transplantation. She developed hemoptysis after the introduction of i.v. epoprostenol, which was administered as a bridging treatment while the patient awaited lung transplantation. She continued to suffer from recurrent hemoptysis, even after switching from i.v. epoprostenol to i.v. treprostinil. Angiography of the systemic and pulmonary arteries revealed the vessel responsible for the recurrent hemoptysis and pulmonary artery embolization was successfully performed...
October 11, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28922964/oral-treprostinil-in-the-treatment-of-pulmonary-arterial-hypertension
#15
Jeremy Feldman, Naomi Habib, John Radosevich, Mohan Dutt
Pulmonary arterial hypertension (PAH) is a rare disease resulting in progressive remodeling of the pulmonary vasculature and eventual right ventricular failure. Despite the development of 13 therapies for PAH since 2000, the use of continuously infused prostanoids retains a special role. Infused medications present unique challenges, and the search for an efficacious oral prostanoid culminated in the FDA approval of oral treprostinil - a first in class oral prostanoid medication approved to treat pulmonary arterial hypertension (PAH)...
October 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28904003/preclinical-pharmacology-and-pharmacokinetics-of-inhaled-hexadecyl-treprostinil-c16tr-a-pulmonary-vasodilator-prodrug
#16
Michel R Corboz, Zhili Li, Vladimir Malinin, Adam J Plaunt, Donna M Konicek, Franziska G Leifer, Kuan-Ju Chen, Charles E Laurent, Han Yin, Marzena C Biernat, Dany Salvail, Jianguo Zhuang, Fadi Xu, Aidan Curran, Walter R Perkins, Richard W Chapman
This report 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 µM) in receptor binding and enzyme inhibition assays including binding to EP2, DP1, IP and EP4; TRE potently bound to each of these prostanoid receptors. C16TR had no effect (up to 200 nM) on platelet aggregation induced by adenosine diphosphate (ADP) in rat blood...
September 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28891448/a-special-focus-on-selexipag-treatment-of-pulmonary-arterial-hypertension
#17
Louise Marqvard Sørensen, Markus Wehland, Marcus Krüger, Ulf Simonsen, Mohamed Zakaria Nassef, Manfred Infanger, Daniela Grimm
BACKGROUND: This review focuses on the treatment of pulmonary arterial hypertension (PAH) with selexipag and compares its drug-related therapeutic effects with those of prostacyclin analogues. METHODS: We searched the relevant literature and summarized the current clinical trials concerning selexipag and PAH. RESULTS: With only few cases per million, PAH is a rare disease, but when untreated it can be life threatening. PAH is linked to elevated levels of endothelin (ET-1) and decreased levels of nitric oxide (NO) and prostacyclin (PGI2)...
September 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28851689/the-second-generation-pgi2-analogue-treprostinil-fails-to-chemoprevent-tumors-in-a-murine-lung-adenocarcinoma-model
#18
Lori Dwyer-Nield, Gregory A Hickey, Micah Friedman, Kevin Choo, Debbie G McArthur, Meredith A Tennis, Melissa L New, Mark Geraci, Robert L Keith
Prostacyclin (prostaglandin I2, PGI2) overproduction in FVB/N mice prevents the formation of carcinogen and tobacco smoke-induced adenomas, and administration of the oral prostacyclin analogue iloprost to wild-type mice also prevented carcinogen-induced mouse lung adenoma formation. Former smokers taking oral iloprost showed improved bronchial dysplasia histology compared with placebo. Next-generation oral prostacyclin analogues, like treprostinil, were developed for the treatment of pulmonary arterial hypertension (PAH)...
August 29, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28840065/management-of-acute-subdural-hematoma-in-a-patient-with-portopulmonary-hypertension-on-prostanoid-therapy
#19
Richard Rammo, Adam Robin, Jessin John, Aqueel Pabaney, Panayiotis Varelas, Max Kole
BACKGROUND: Treprostinil is a prostacyclin analog used to treat portopulmonary hypertension (PPHTN) and is one of several drugs shown to increase survival, but results in platelet dysfunction. Little is known about the management of patients on treprostinil who present with an acute subdural hematoma (aSDH). We describe such a case and offer our recommendations on management based on our experience and review of the literature. CASE DESCRIPTION: A 63-year-old, right-handed female with a history of PPHTN presented with severe headache and was found to have a large left aSDH with midline shift on imaging...
2017: Surgical Neurology International
https://www.readbyqxmd.com/read/28680576/recommendations-for-the-use-of-oral-treprostinil-in-clinical-practice-a-delphi-consensus-project-pulmonary-circulation
#20
Franck F Rahaghi, Jeremy P Feldman, Roblee P Allen, Victor Tapson, Zeenat Safdar, Vijay P Balasubramanian, Shelley Shapiro, Michael A Mathier, Jean M Elwing, Murali M Chakinala, R James White
Oral treprostinil was recently labeled for treatment of pulmonary arterial hypertension. Similar to the period immediately after parenteral treprostinil was approved, there is a significant knowledge gap for practicing physicians who might prescribe oral treprostinil. Despite its oral route of delivery, use of the drug is challenging because of the requirement for careful titration and management of drug-related adverse effects. We aimed to create a consensus document combining available evidence with expert opinion to provide guidance for use of oral treprostinil...
March 2017: Pulmonary Circulation
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