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Ambrisentan

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https://www.readbyqxmd.com/read/29341047/german-guideline-for-idiopathic-pulmonary-fibrosis-update-on-pharmacological-therapies-2017
#1
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...
January 16, 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
#2
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...
December 16, 2017: 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
#3
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...
December 27, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29251556/express-the-impact-of-ambrisentan-and-tadalafil-upfront-combination-therapy-on-cardiac-function-in-patients-with-scleroderma-associated-pulmonary-arterial-hypertension-cardiac-magnetic-resonance-feature-tracking-study
#4
https://www.readbyqxmd.com/read/29215546/initial-tadalafil-and-ambrisentan-combination-therapy-in-pulmonary-arterial-hypertension-clinical-and-haemodynamic-long-term-efficacy-italy-study
#5
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
#6
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
#7
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-pulmonary-arterial-hypertension
#8
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.
June 29, 2017: 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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28425346/ambrisentan-a-review-of-its-use-in-pulmonary-arterial-hypertension
#16
Belinda N Rivera-Lebron, Michael G Risbano
Pulmonary arterial hypertension (PAH) is a progressive disease defined by an elevation in pulmonary arterial pressure that can lead to right heart failure and death. Ambrisentan is a selective endothelin receptor antagonist approved for the treatment of idiopathic, heritable PAH and connective tissue disease-associated PAH. Ambrisentan has been shown to improve exercise capacity and hemodynamics with an acceptable side-effect profile. It has also proven to be safely used in combination with other PAH-specific medications, especially with phosphodiesterase-5 inhibitors...
June 2017: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/28369585/from-the-cover-mechanisticinsights-in-cytotoxic-and-cholestatic-potential-of-the-endothelial-receptor-antagonists-using-heparg-cells
#17
Matthew Gibson Burbank, Ahmad Sharanek, Audrey Burban, Hervé Mialanne, Hélène Aerts, Christiane Guguen-Guillouzo, Richard John Weaver, André Guillouzo
Several endothelin receptor antagonists (ERAs) have been developed for the treatment of pulmonary arterial hypertension (PAH). Some of them have been related to clinical cases of hepatocellular injury (sitaxentan [SIT]) and/or cholestasis (bosentan [BOS]). We aimed to determine if ambrisentan (AMB) and macitentan (MAC), in addition to BOS and SIT, could potentially cause liver damage in man by use of human HepaRG cells. Our results showed that like BOS, MAC-induced cytotoxicity and cholestatic disorders characterized by bile canaliculi dilatation and impairment of myosin light chain kinase signaling...
June 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28348949/impact-of-advanced-medical-therapy-for-the-outcome-of-an-adult-patient-with-eisenmenger-syndrome
#18
Eglė Ereminienė, Marija Kinderytė, Skaidrius Miliauskas
Eisenmenger syndrome (ES) is the most severe form of pulmonary arterial hypertension (PAH) associated with congenital heart disease. It is an extremely devastating condition with a serious impact on patients' life. Classical therapy of ES remains directed to avoid complications, such as erythrocytosis, treatment of congestive heart failure, prevention of infection, and secondary haematological abnormalities such as iron deficiency and coagulation disorders. However, the only effective treatment is heart-lung transplantation; still, morbidity and mortality after transplantation remain substantially high...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28348063/long-term-endothelin-a-receptor-antagonism-provides-robust-renal-protection-in-humanized-sickle-cell-disease-mice
#19
Malgorzata Kasztan, Brandon M Fox, Joshua S Speed, Carmen De Miguel, Eman Y Gohar, Tim M Townes, Abdullah Kutlar, Jennifer S Pollock, David M Pollock
Sickle cell disease (SCD)-associated nephropathy is a major source of morbidity and mortality in patients because of the lack of efficacious treatments targeting renal manifestations of the disease. Here, we describe a long-term treatment strategy with the selective endothelin-A receptor (ETA) antagonist, ambrisentan, designed to interfere with the development of nephropathy in a humanized mouse model of SCD. Ambrisentan preserved GFR at the level of nondisease controls and prevented the development of proteinuria, albuminuria, and nephrinuria...
August 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28300593/functional-estimation-of-endothelin-1-receptor-antagonism-by-bosentan-macitentan-and-ambrisentan-in-human-pulmonary-and-radial-arteries-in-vitro
#20
James A Angus, Paul F Soeding, Richard J A Hughes, Christine E Wright
BACKGROUND: Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ETA-receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically-approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro. METHODS: Human isolated pulmonary (i...
June 5, 2017: European Journal of Pharmacology
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