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Ambrisentan

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https://www.readbyqxmd.com/read/28628863/simultaneous-quantification-of-endothelin-receptor-antagonists-and-phosphodiesterase-5-inhibitors-currently-used-in-pulmonary-arterial-hypertension
#1
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...
June 10, 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
#2
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
#3
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
#4
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
#5
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...
May 30, 2017: Pneumologie
https://www.readbyqxmd.com/read/28494463/plasma-drug-concentrations-in-patients-with-pulmonary-arterial-hypertension-on-combination-treatment
#6
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
#7
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
#8
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...
April 1, 2017: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/28369585/mechanistic-insights-in-cytotoxic-and-cholestatic-potential-of-the-endothelial-receptor-antagonists-using-heparg-cells
#9
Matthew Gibson Burbank, Ahmad Sharanek, Audrey Burban, Hervé Mialanne, Hélène Aerts, Christiane Guguen-Guillouzo, Richard John Weaver, André Guillouzo
Several endothelin receptor antagonists have been developed for the treatment of pulmonary arterial hypertension. Some of them have been related to clinical cases of hepatocellular injury (sitaxentan) and/or cholestasis (bosentan). We aimed to determine if ambrisentan and macitentan, in addition to bosentan and sitaxentan, could potentially cause liver damage in man by use of human HepaRG cells. Our results showed that like bosentan, macitentan induced cytotoxicity and cholestatic disorders characterized by bile canaliculi dilatation and impairment of myosin light chain kinase signaling...
March 24, 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
#10
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
#11
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...
March 27, 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
#12
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
https://www.readbyqxmd.com/read/28223322/endothelin-eta-receptor-blockade-by-activating-etb-receptors-increases-vascular-permeability-and-induces-exaggerated-fluid-retention
#13
Magali Vercauteren, Frederic Trensz, Anne Pasquali, Christophe Cattaneo, Daniel S Strasser, Patrick Hess, Marc Iglarz, Martine Clozel
Endothelin (ET) receptor antagonists have been associated with fluid retention. It has been suggested that, of the two endothelin receptor subtypes, ETB receptors should not be blocked, because of their involvement in natriuresis and diuresis. Surprisingly, clinical data suggest that ETA-selective antagonists pose a greater risk of fluid overload than dual antagonists. The purpose of this study was to evaluate the contribution of each endothelin receptor to fluid retention and vascular permeability in rats...
May 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28217316/subacute-right-heart-failure-revealing-three-simultaneous-causes-of-post-embolic-pulmonary-hypertension-in-metastatic-dissemination-of-breast-cancer
#14
Flavien Vincent, Nicolas Lamblin, Marion Classe, Guillaume Schurtz, Antoine Rauch, Marie Fertin, Pascal De Groote
A 72-year-old woman with history of breast cancer only treated surgically was referred to our department for pulmonary hypertension (PH) suspicion. Echocardiogram revealed elevated right ventricular systolic pressure. Computed tomography (CT) angiogram showed no pulmonary embolism (PE), but lung scan revealed two ventilation-perfusion mismatch areas. Right cardiac catheterization established precapillary PH. Despite treatment with PH specific therapy (sildenafil, ambrisentan, and epoprostenol), her condition worsened rapidly with acute right heart failure (RHF)...
February 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28131522/combined-approach-using-capillary-electrophoresis-nmr-and-molecular-modeling-for-ambrisentan-related-substances-analysis-investigation-of-intermolecular-affinities-complexation-and-separation-mechanism
#15
Benedetta Pasquini, Fabrizio Melani, Claudia Caprini, Massimo Del Bubba, Sergio Pinzauti, Serena Orlandini, Sandra Furlanetto
A comprehensive investigation on the CE separation mechanisms and on the inclusion complexation with CyDs of the chiral drug S-ambrisentan (S-AMB), its R-enantiomer and other impurities was performed by different techniques. A CE method was previously set up allowing the simultaneous determination of the enantiomeric purity and of impurities of S-AMB, based on the addition of SDS micelles and γ-cyclodextrin (γCyD) to borate buffer. In this study, the electrophoretic behavior of the analytes in terms of selectivity and mobility with respect to the addition of different CyDs was first investigated, evidencing the presence of interactions for all the CyDs, but the unique ability of γCyD for obtaining the separation of all the compounds...
January 21, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28123500/effects-of-low-dose-tolvaptan-on-electrolyte-abnormality-and-hemodynamic-parameters-in-a-liver-cirrhosis-associated-portopulmonary-hypertension-patient-a-case-report
#16
Yoshito Ogihara, Norikazu Yamada, Kaoru Dohi, Akimasa Matsuda, Satoshi Ota, Ken Ishikura, Mashio Nakamura, Masaaki Ito
The present study reported a case of portopulmonary hypertension (POPH) that was secondary to underlying liver cirrhosis in a 58-year-old woman, who was successfully treated with low-dose tolvaptan. The patient had suffered from refractory peripheral edema and electrolyte abnormalities, including severe hypokalemia, under the combination therapy of sildenafil, ambrisentan, furosemide and spironolactone. Subsequent to the initiation of low-dose tolvaptan at 3.75 mg/day with concurrent de-escalation of the dose of furosemide, the daily urine volume increased, peripheral edema improved and the serum potassium level increased immediately...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28039187/initial-combination-therapy-with-ambrisentan-and-tadalafil-in-connective-tissue-disease-associated-pulmonary-arterial-hypertension-ctd-pah-subgroup-analysis-from-the-ambition-trial
#17
John Gerry Coghlan, Nazzareno Galiè, Joan Albert Barberà, Adaani E Frost, Hossein-Ardeschir Ghofrani, Marius M Hoeper, Masataka Kuwana, Vallerie V McLaughlin, Andrew J Peacock, Gérald Simonneau, Jean-Luc Vachiéry, Christiana Blair, Hunter Gillies, Karen L Miller, Julia H N Harris, Jonathan Langley, Lewis J Rubin
BACKGROUND: Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. OBJECTIVE: To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial...
December 30, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27974976/sinus-venosus-atrial-septal-defect-complicated-by-eisenmenger-syndrome-and-the-role-of-vasodilator-therapy
#18
Amornpol Anuwatworn, Maheedhar Gedela, Edgard Bendaly, Julia A Prescott-Focht, Jimmy Yee, Richard Clark, Orvar Jonsson
Sinus venosus atrial septal defect is a rare congenital, interatrial communication defect at the junction of the right atrium and the vena cava. It accounts for 5-10% of cases of all atrial septal defects. Due to the rare prevalence and anatomical complexity, diagnosing sinus venous atrial septal defects poses clinical challenges which may delay diagnosis and treatment. Advanced cardiac imaging studies are useful tools to diagnose this clinical entity and to delineate the anatomy and any associated communications...
2016: Case Reports in Cardiology
https://www.readbyqxmd.com/read/27927914/tryptophan-hydroxylase-1-inhibition-impacts-pulmonary-vascular-remodeling-in-two-rat-models-of-pulmonary-hypertension
#19
Robert J Aiello, Patricia-Ann Bourassa, Qing Zhang, Jeffrey Dubins, Daniel R Goldberg, Stéphane De Lombaert, Marc Humbert, Christophe Guignabert, Maria A Cavasin, Timothy A McKinsey, Vishwas Paralkar
Pulmonary arterial hypertension (PAH) is a progressive disease defined by a chronic elevation in pulmonary arterial pressure with extensive pulmonary vascular remodeling and perivascular inflammation characterized by an accumulation of macrophages, lymphocytes, dendritic cells, and mast cells. Although the exact etiology of the disease is unknown, clinical as well as preclinical data strongly implicate a role for serotonin (5-HT) in the process. Here, we investigated the chronic effects of pharmacological inhibition of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in peripheral 5-HT biosynthesis, in two preclinical models of pulmonary hypertension (PH), the monocrotaline (MCT) rat and the semaxanib (SUGEN, Medinoah, Suzhou, China)-hypoxia rat...
February 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27912207/clinical-adverse-effects-of-endothelin-receptor-antagonists-insights-from-the-meta-analysis-of-4894-patients-from-24-randomized-double-blind-placebo-controlled-clinical-trials
#20
Anhua Wei, Zhichun Gu, Juan Li, Xiaoyan Liu, Xiaofan Wu, Yi Han, Jun Pu
BACKGROUND: Evidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta-analysis. METHODS AND RESULTS: After systematic searches of the Medline, Embase, and Cochrane Library databases and the ClinicalTrials.gov website, randomized controlled trials with patients receiving ERAs (bosentan, macitentan, or ambrisentan) in at least 1 treatment group were included. All reported adverse events of ERAs were evaluated...
October 26, 2016: Journal of the American Heart Association
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