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Ambrisentan

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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
#1
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...
March 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28223322/eta-receptors-blockade-by-activating-etb-receptors-increases-vascular-permeability-and-induces-exaggerated-fluid-retention
#2
Magali Vercauteren, Frederic Trensz, Anne Pasquali, Christophe Cattaneo, Daniel S Strasser, Patrick Hess, Marc Iglarz, Martine Clozel
Endothelin 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. Sitaxentan and ambrisentan as ETA-selective antagonists, bosentan and macitentan as dual antagonists were used as representatives of each class, respectively...
February 21, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27770771/evaluation-of-efficacy-safety-and-tolerability-of-ambrisentan-in-chinese-adults-with-pulmonary-arterial-hypertension-a-prospective-open-label-cohort-study
#10
Y Huo, Z C Jing, X F Zeng, J M Liu, Z X Yu, G C Zhang, Y Li, Y Wang, Q S Ji, P Zhu, B X Wu, Y Zheng, P P Wang, J Li
BACKGROUND: Although several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH. METHODS: Eligible patients with PAH (World Health Organisation [WHO] functional class [FC] II orIII) were enrolled and received Ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period (dose titration to 10 mgallowed)...
October 22, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27745818/initial-combination-therapy-with-ambrisentan-and-tadalafil-and-mortality-in-patients-with-pulmonary-arterial-hypertension-a-secondary-analysis-of-the-results-from-the-randomised-controlled-ambition-study
#11
Marius M Hoeper, Vallerie V McLaughlin, Joan Albert Barberá, Adaani E Frost, Hossein-Ardeschir Ghofrani, Andrew J Peacock, Gérald Simonneau, Stephan Rosenkranz, Ronald J Oudiz, R James White, Karen L Miller, Jonathan Langley, Julia H N Harris, Christiana Blair, Lewis J Rubin, Jean-Luc Vachiery
BACKGROUND: In treatment-naive patients with pulmonary arterial hypertension, initial combination therapy with ambrisentan and tadalafil reduces the risk of clinical failure events compared with monotherapy. We did this secondary analysis to further investigate the effect of combination therapy on survival. METHODS: We analysed survival data from the modified intention-to-treat population of the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) trial...
October 10, 2016: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27574547/antifibrotic-effects-of-ambrisentan-an-endothelin-a-receptor-antagonist-in-a-non-alcoholic-steatohepatitis-mouse-model
#12
Toshiaki Okamoto, Masahiko Koda, Kennichi Miyoshi, Takumi Onoyama, Manabu Kishina, Tomomitsu Matono, Takaaki Sugihara, Keiko Hosho, Junichi Okano, Hajime Isomoto, Yoshikazu Murawaki
AIM: To examine the effects of the endothelin type A receptor antagonist ambrisentan on hepatic steatosis and fibrosis in a steatohepatitis mouse model. METHODS: Fatty liver shionogi (FLS) FLS-ob/ob mice (male, 12 wk old) received ambrisentan (2.5 mg/kg orally per day; n = 8) or water as a control (n = 5) for 4 wk. Factors were compared between the two groups, including steatosis, fibrosis, inflammation, and endothelin-related gene expression in the liver. RESULTS: In the ambrisentan group, hepatic hydroxyproline content was significantly lower than in the control group (18...
August 8, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27506903/systematic-review-of-randomized-controlled-trials-of-endothelin-receptor-antagonists-for-pulmonary-arterial-hypertension
#13
REVIEW
Michael Kuntz, Miguel M Leiva-Juarez, Suvitesh Luthra
BACKGROUND: There are currently three Food and Drug Administration approved endothelin receptor antagonists (ERAs): bosentan, ambrisentan, and macitentan. There is a growing body of evidence that demonstrates the beneficial effects of ERAs in patients with pulmonary arterial hypertension (PAH). OBJECTIVES: To compare the available evidence from randomized clinical trials for specific outcomes of different endothelin antagonists for the treatment of PAH. METHODS: A multi-database search of randomized controlled trials up to March 15, 2016 was conducted for those that would measure functional parameters of patients with PAH treated with ERA monotherapy versus placebo...
October 2016: Lung
https://www.readbyqxmd.com/read/27492539/ambrisentan-response-in-connective-tissue-disease-associated-pulmonary-arterial-hypertension-ctd-pah-a-subgroup-analysis-of-the-aries-e-clinical-trial
#14
Aryeh Fischer, Christopher P Denton, Marco Matucci-Cerinic, Hunter Gillies, Christiana Blair, James Tislow, Steven D Nathan
OBJECTIVE: Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and early mortality and is an important complication in patients with connective tissue disease (CTD). Previously, the endothelin A selective receptor antagonist, ambrisentan, demonstrated efficacy and safety in treating patients with PAH due to WHO Group I etiologies. These analyses describe the 3-year efficacy and safety of ambrisentan in patients specifically with CTD associated PAH (CTD-PAH)...
August 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27434819/new-paradigm-for-pulmonary-arterial-hypertension-treatment
#15
Yuichi Tamura, Richard N Channick
PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) was previously considered a uniformly fatal disease, with patients succumbing to right heart failure and death at an average of 3 years after diagnosis. The past 20 years, however, have seen the development of numerous targeted therapies that have changed the natural history of PAH. As more pharmacologic agents have been approved and utilized, further advances in the design of and endpoints for clinical trials. This study will review some of these notable developments...
September 2016: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/27425759/enantioseparation-and-impurity-determination-of-ambrisentan-using-cyclodextrin-modified-micellar-electrokinetic-chromatography-visualizing-the-design-space-within-quality-by-design-framework
#16
S Orlandini, B Pasquini, C Caprini, M Del Bubba, M Douša, S Pinzauti, S Furlanetto
A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity and of impurities of the chiral drug ambrisentan has been developed following the Quality by Design principles. The selected separation system consisted of a micellar pseudostationary phase made by sodium dodecyl sulphate with the addition of γ-cyclodextrin. The effects of critical process parameters (capillary length, temperature, voltage, borate concentration, pH, sodium dodecyl sulphate concentration, γ-cyclodextrin concentration) on enantioresolution of ambrisentan and analysis time were extensively investigated by multivariate strategies involving a screening phase and Response Surface Methodology...
October 7, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27422754/tnf%C3%AE-induced-airway-smooth-muscle-cell-proliferation-depends-on-endothelin-receptor-signaling-gm-csf-and-il-6
#17
Jürgen Knobloch, Sarah Derya Yanik, Sandra Körber, Erich Stoelben, David Jungck, Andrea Koch
UNLABELLED: Pathological proliferation of human airway smooth muscle cells (HASMCs) causes hyperplasia in chronic lung diseases. Signaling pathways that link airway inflammation to HASMC proliferation might provide therapeutic targets for the prevention of airway remodeling and chronic lung diseases. Endothelin-1 (ET-1) signals via endothelin-A- and B-receptors (ETAR, ETBR) to perpetuate HASMC-associated and TNFα-dependent inflammatory processes. HYPOTHESIS: endothelin receptor antagonists (ERAs) suppress HASMC proliferation induced by inflammatory cytokines...
September 15, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27321813/from-bosentan-tracleer%C3%A2-to-macitentan-opsumit%C3%A2-the-medicinal-chemistry-perspective
#18
REVIEW
Christoph Boss, Martin H Bolli, John Gatfield
The endothelin peptides bind to two receptors found on cells of vasculature and in tissues. While the endothelin-A (ETA)-receptor is predominantly expressed in vascular smooth muscle cells, the endothelin-B (ETB)-receptor is also found in endothelial cells, fibroblasts, and neuronal cells. Activation of the endothelin system plays a driving role in several chronic cardiovascular diseases and several endothelin receptor antagonists (ERAs) (bosentan (6), ambrisentan (83) and macitentan (43)) have successfully been introduced as oral treatments for the life threatening condition of pulmonary arterial hypertension (PAH)...
August 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27282418/ambrisentan-use-for-pulmonary-arterial-hypertension-in-a-post-authorization-drug-registry-the-volibris-tracking-study
#19
Jean-Luc Vachiéry, Marius M Hoeper, Andrew J Peacock, Olivier Sitbon, Martino Cheli, Colin Church, Karen M Olsson, Massimiliano Palazzini, Brian Waterhouse, Jonathan Langley, Nazzareno Galié
BACKGROUND: The VOLibris Tracking (VOLT) Study was an open-label, prospective, observational, multicenter, post-marketing registry program designed to more fully characterize the safety profile of ambrisentan for the treatment of pulmonary arterial hypertension (PAH). The key outcome was the incidence of aminotransferase elevations >3× the upper limit of normal (ULN). METHODS: In total, 999 patients from 115 centers in 15 countries, who were prescribed ambrisentan for the treatment of PAH (Functional Class II and III) between 30 June 2008 and 13 May 2011, were enrolled...
May 6, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27240565/simultaneous-determination-of-bosentan-glimepiride-hybos-and-m1-in-rat-plasma-by-uplc-ms-ms-and-its-application-to-pharmacokinetic-study
#20
Mengchun Chen, Wenjie Song, Shuanghu Wang, Qiulei Chen, Peipei Pan, Tao Xu, Guoxin Hu, Zhiqiang Zheng
A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the simultaneous determination of bosentan (BOS), glimepiride (GLP), hydroxyl bosentan (HYBOS) and hydroxyl glimepiride (M1) in rat plasma using one-step protein precipitation was developed and validated. After addition of ambrisentan as an internal standard (IS), protein precipitation by acetonitrile was used in sample preparation. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column (2...
August 2016: Journal of Chromatographic Science
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