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Ambrisentan

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https://www.readbyqxmd.com/read/29719121/a-focus-on-macitentan-in-the-treatment-of-pulmonary-arterial-hypertension
#1
Martin Bedan, Daniela Grimm, Markus Wehland, Ulf Simonsen, Manfred Infanger, Marcus Krüger
The approval of macitentan has increased the number of pharmacological treatments of pulmonary arterial hypertension (PAH). Here, we review the effect on PAH of macitentan compared to other endothelin receptor antagonists (ERAs). Drugs targeting the endothelin (ET) pathway include the selective ETA receptor antagonist ambrisentan, the ETA /ETB receptor antagonists bosentan and macitentan which were recently approved for PAH treatment. This article is protected by copyright. All rights reserved.
May 2, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29684813/metabolite-characterization-of-ambrisentan-in-in-vitro-and-in-vivo-matrices-by-uhplc-qtof-ms-ms-detection-of-glutathione-conjugate-of-epoxide-metabolite-evidenced-by-in-vitro-gsh-trapping-assay
#2
P Johnsi Rani, Chiguru Vishnuvardhan, Rakesh D Nimbalkar, Prabha Garg, N Satheeshkumar
The focus of the present study is on in vitro and in vivo metabolite identification of ambrisentan (AMBR) a selective endothelin type - A (ETA) receptor antagonist using quadruple time-of-flight mass spectrometry (QTOF/MS). in vitro metabolism study was conducted by incubating AMBR in rat liver microsomes (RLM), rat and human liver S9 fractions. In vivo study was carried out through the collection of urine, faeces and plasma samples at various time points after oral administration of AMBR in suspension form at a dose of 25 mg/kg to six male Sprague - Dawley (SD) rats...
April 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29607828/t-cell-large-granular-lymphocytic-leukemia-with-pulmonary-hypertension
#3
Sidra Khalid, Hamed Daw, Miriam Jacob, Megan Nakashima
T cell large granular lymphocytic leukemia is a hematological disorder which is characterized by the proliferation of CD 3+ cytotoxic T cells. We present a case about a patient who was diagnosed with T cell large granular lymphocytic leukemia and then developed pulmonary hypertension. He was treated for his leukemia with methotrexate and simultaneously treated for his pulmonary hypertension with selexipag and ambrisentan. As his leukemia improved, we also noticed an improvement in his pulmonary hypertension from a NYHA class IV to class I...
January 2018: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/29475138/novel-polymorph-of-ambrisentan-characterization-and-stability
#4
Jamshed Haneef, Renu Chadha, Vijay Gupta, Sanjay K Mandal
The present work highlights a novel polymorph (form II) of ambrisentan (AMT), a selective endothelin type A (ETA) receptor antagonist used in the treatment of pulmonary arterial hypertension (PAH). Form II was isolated by solution crystallization and characterised by differential scanning calorimetry, powder X-ray diffraction, solution calorimetry and aqueous solubility. The single crystal X-ray diffraction shows that it crystallizes in monoclinic system with space group P21/c different from the form I (commercial form)...
May 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29436260/treatment-patterns-and-associated-health-care-costs-before-and-after-treatment-initiation-among-pulmonary-arterial-hypertension-patients-in-the-united-states
#5
Charles D Burger, A Burak Ozbay, Howard M Lazarus, Ellen Riehle, Leslie B Montejano, Gregory Lenhart, R James White
BACKGROUND: Despite multiple treatment options, the prognosis of pulmonary arterial hypertension (PAH) remains poor. PAH patients experience a high economic burden due to comorbidities, hospitalizations, and medication costs. Although combination therapy has been shown to reduce hospitalizations, the relationship between treatment, health care utilization, and costs remains unclear. OBJECTIVE: To provide a characterization of health care utilization and costs in real-world settings by comparing periods before and after initiating PAH-specific treatment...
February 13, 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29341047/german-guideline-for-idiopathic-pulmonary-fibrosis-update-on-pharmacological-therapies-2017
#6
Jürgen Behr, Andreas Günther, Francesco Bonella, Klaus Geißler, Dirk Koschel, Michael Kreuter, Antje Prasse, Nicolas Schönfeld, Helmut Sitter, Joachim Müller-Quernheim, Ulrich Costabel
Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan...
February 2018: Pneumologie
https://www.readbyqxmd.com/read/29289894/bionalytical-validation-study-for-the-determination-of-unbound-ambrisentan-in-human-plasma-using-rapid-equilibrium-dialysis-followed-by-ultra-performance-liquid-chromatography-coupled-to-mass-spectrometry
#7
Soledad Garcia-Martínez, Estitxu Rico, Enriqueta Casal, Alba Grisaleña, Eider Alcaraz, Nicholas King, Nerea Leal, Iker Navarro, Miguel Ángel Campanero
Ambrisentan is a highly selective endothelin-1 type A receptor antagonist indicated for use in the treatment of pulmonary hypertension. In this study an assay was developed and validated for the quantification of total and unbound (free) concentrations of ambrisentan in human plasma. Plasma samples were dialysed against phosphate buffered saline in a rapid equilibrium dialysis device to obtain dialysate and plasma for unbound and total ambrisentan, respectively. Subsequently, ambrisentan and deuterated ambrisentan (internal standard) were extracted from plasma or plasma dialysate by solid-phase extraction and separated by ultra performance liquid chromatography using on a reversed-phase C18 column...
February 20, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29282676/surveillance-on-the-safety-and-efficacy-of-ambrisentan-volibris-tablet-2-5-mg-in-patients-with-pulmonary-arterial-hypertension-in-real-clinical-practice-post-marketing-surveillance-interim-analysis-report
#8
Tomohiko Takahashi, Satoru Hayata, Akihiro Kobayashi, Yuna Onaka, Takeshi Ebihara, Terufumi Hara
BACKGROUND AND OBJECTIVE: Pulmonary arterial hypertension (PAH) is an intractable and rare disease and the accumulation of clinical evidence under real-world setting is needed. A post-marketing surveillance for the endothelin receptor antagonist ambrisentan (Volibris tablet) has been conducted by all-case investigation since September 2010. This paper is an interim report on the safety and efficacy of ambrisentan in 702 patients with PAH. METHODS: PAH patients aged 15 years or older were subjected to the analysis...
March 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29251556/the-impact-of-ambrisentan-and-tadalafil-upfront-combination-therapy-on-cardiac-function-in-scleroderma-associated-pulmonary-arterial-hypertension-patients-cardiac-magnetic-resonance-feature-tracking-study
#9
Takahiro Sato, Bharath Ambale-Venkatesh, Joao A C Lima, Stefan L Zimmerman, Ryan J Tedford, Tomoki Fujii, Olivia L Hulme, Erica H Pullins, Celia P Corona-Villalobos, Roham T Zamanian, Omar A Minai, Reda E Girgis, Kelly Chin, Rubina Khair, Rachel L Damico, Todd M Kolb, Stephen C Mathai, Paul M Hassoun
The aim of this study was to evaluate the effect of upfront combination therapy with ambrisentan and tadalafil on left ventricular (LV) and right ventricular (RV) function in patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). LV and RV peak longitudinal and circumferential strain and strain rate (SR), which consisted of peak systolic SR (SRs), peak early diastolic SR (SRe), and peak atrial-diastolic SR (SRa) were analyzed using cardiac magnetic resonance imaging (CMRI) data from the recently published ATPAHSS-O trial (ambrisentan and tadalafil upfront combination therapy in SSc-PAH)...
January 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29215546/initial-tadalafil-and-ambrisentan-combination-therapy-in-pulmonary-arterial-hypertension-clinical-and-haemodynamic-long-term-efficacy-italy-study
#10
Michele D'Alto, Emanuele Romeo, Paola Argiento, Giuseppe Paciocco, Renato Prediletto, Stefano Ghio, Michele Correale, Francesco Lo Giudice, Roberto Badagliacca, Alessandra Greco, Carmine Dario Vizza
AIMS: Initial combination therapy with ambrisentan and tadalafil (upfront therapy) offers clinical benefits in pulmonary arterial hypertension (PAH) and reduces the risk of clinical failure compared with monotherapy in naïve patients. The aim of study is to assess the efficacy of a 12-month upfront therapy with ambrisentan and tadalafil in improving haemodynamics in incident PAH patients. METHODS: This is a multicentre retrospective analysis of real-world Italian clinical data in 56 patients with newly diagnosed PAH...
January 2018: Journal of Cardiovascular Medicine
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
#11
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/28857147/safety-and-ergogenic-properties-of-combined-aminophylline-and-ambrisentan-in-hypoxia
#12
Thies Schroeder, Claude A Piantadosi, Michael J Natoli, Julie Autmizguine, Michael Cohen-Wolkowieczs, Karyn L Hamilton, Christopher Bell, Jelena Klawitter, Uwe Christians, David C Irwin, Robert J Noveck
We hypothesized that concomitant pharmacological inhibition of the endothelin and adenosine pathway is safe and improves exercise performance in hypoxic humans, via a mechanism that does not involve augmentation of blood oxygenation. To test this hypothesis, we established safety and drug interactions for aminophylline (500 mg) plus ambrisentan (5 mg) in normoxic volunteers. Subsequently, a placebo-controlled study was employed to test the combination in healthy resting and exercising volunteers at simulated altitude (4,267 m)...
August 31, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28661697/improvement-in-right-ventricular-strain-with-ambrisentan-and-tadalafil-upfront-therapy-in-scleroderma-associated-pulmonary-arterial-hypertension
#13
Valentina Mercurio, Monica Mukherjee, Ryan J Tedford, Roham T Zamanian, Rubina M Khair, Takahiro Sato, Omar A Minai, Fernando Torres, Reda E Girgis, Kelly Chin, Rachel Damico, Todd M Kolb, Stephen C Mathai, Paul M Hassoun
No abstract text is available yet for this article.
February 1, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28628863/simultaneous-quantification-of-endothelin-receptor-antagonists-and-phosphodiesterase-5-inhibitors-currently-used-in-pulmonary-arterial-hypertension
#14
Yeliz Enderle, Lukas Witt, Heinrike Wilkens, Ekkehard Grünig, Walter E Haefeli, Jürgen Burhenne
Combination treatment with endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitors (PDE5I) improved efficacy of pulmonary arterial hypertension (PAH) therapy. However, drug-drug interactions, variable exposure, non-adherence can influence plasma levels. For these reasons, drug quantification may be advantageous particularly in patients with poor treatment responses. We developed, validated, and applied an assay for the simultaneous quantification of ambrisentan, bosentan, macitentan, sildenafil, and tadalafil as well as their main (and partly active) metabolites in human plasma...
September 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28605810/a-compact-whole-eye-perfusion-system-to-evaluate-pharmacologic-responses-of-outflow-facility
#15
Enhua H Zhou, Michael Paolucci, Thaddeus P Dryja, Ted Manley, Chuanxi Xiang, Dennis S Rice, Ganesh Prasanna, Amy Chen
Purpose: To discover novel therapies that lower IOP by increasing aqueous humor outflow facility, ex vivo ocular perfusion systems provide a valuable tool. However, currently available designs are limited by their throughput. Here we report the development of a compact, scalable perfusion system with improved throughput and its validation using bovine and porcine eyes. Methods: At a fixed IOP of 6 mm Hg, flow rate was measured by flow sensors. We validated the system by measuring the outflow responses to Y-39983 (a Rho kinase inhibitor), endothelin-1 (ET-1), ambrisentan (an antagonist for endothelin receptor A [ETA]), sphigosine-1-phosphate (S1P), JTE-013 (antagonist for S1P receptor 2 [S1P2]), S-nitroso-N-acetylpenicillamine (SNAP, a nitric oxide [NO] donor), and 3-Morpholino-sydnonimine (SIN-1, another NO donor)...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28597769/a-systematic-review-of-transition-studies-of-pulmonary-arterial-hypertension-specific-medications
#16
Avraham Sofer, Michael J Ryan, Ryan J Tedford, Joel A Wirth, Wassim H Fares
Pulmonary arterial hypertension (PAH) is a progressive potentially fatal disease. Multiple pharmacologic options are now available, which facilitated transitions between different therapeutic options, although the evidence for such transitions has not been well described. We sought to review the evidence supporting the safety and/or efficacy of transitioning between PAH-specific medications. We performed a systematic review of all published studies in the Medline database between 1 January 2000 and 30 June 2016 reporting on any transition between the currently Food and Drug Administration (FDA)-approved PAH-specific medications...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28597763/open-label-study-of-ambrisentan-in-patients-with-exercise-pulmonary-hypertension
#17
Sergio A Segrera, Laurie Lawler, Alexander R Opotowsky, David Systrom, Aaron B Waxman
A growing body of evidence suggests that exercise pulmonary hypertension (ePH) is an early form of pulmonary arterial hypertension (PAH). Identifying the disease at an early, potentially more responsive phase, and initiating treatment may improve functional status and prevent progression to severe forms of PAH. This was a single-center, open-label six-month treatment trial to evaluate the effect of ambrisentan on pulmonary hemodynamics and exercise capacity in ePH utilizing invasive cardiopulmonary exercise testing (iCPET)...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28558396/-german-guideline-for-idiopathic-pulmonary-fibrosis-update-on-pharmacological-therapies-2017
#18
Jürgen Behr, Andreas Günther, Francesco Bonella, Klaus Geißler, Dirk Koschel, Michael Kreuter, Antje Prasse, Nicolas Schönfeld, Helmut Sitter, Joachim Müller-Quernheim, Ulrich Costabel
Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan...
July 2017: Pneumologie
https://www.readbyqxmd.com/read/28494463/plasma-drug-concentrations-in-patients-with-pulmonary-arterial-hypertension-on-combination-treatment
#19
Ekkehard Grünig, Johanna Ohnesorge, Nicola Benjamin, Jürgen Burhenne, Yeliz Enderle, Benjamin Egenlauf, Christine Fischer, Satenik Harutyunova, Andrea Huppertz, Hans Klose, Walter E Haefeli
BACKGROUND: Combination therapy with the phosphodiesterase type 5 inhibitors (PDE-5i) sildenafil or tadalafil and the endothelin receptor antagonists (ERA) bosentan, ambrisentan, or macitentan may cause mutual pharmacokinetic interactions in patients with pulmonary arterial hypertension (PAH). OBJECTIVE: The objective of this study was to analyze plasma drug concentrations in PAH patients receiving different combination treatments. METHODS: PAH patients receiving a stable combination treatment with ERA and PDE-5i with targeted dosage for at least 1 month were routinely assessed, including clinical parameters and plasma drug concentrations...
2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28427554/clinical-and-hemodynamic-improvements-after-adding-ambrisentan-to-background-pde5i-therapy-in-patients-with-pulmonary-arterial-hypertension-exhibiting-a-suboptimal-therapeutic-response-athena-1
#20
Shelley Shapiro, Fernando Torres, Jeremy Feldman, Anne Keogh, Martine Allard, Christiana Blair, Hunter Gillies, James Tislow, Ronald J Oudiz
OBJECTIVE: Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and premature death. While recent data supports the initial combination of ambrisentan (a selective ERA) and tadalafil (a PDE5i) in functional class II or III patients, there is no published data describing the safety and efficacy of ambrisentan when added to patients currently receiving a PDE5i and exhibiting a suboptimal response. The ATHENA-1 study describes the safety and efficacy of the addition of ambrisentan in this patient population...
May 2017: Respiratory Medicine
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