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https://www.readbyqxmd.com/read/28639216/biocomparison-study-of-adult-and-paediatric-dose-strengths-of-the-prostacyclin-receptor-agonist-selexipag
#1
Margaux Boehler, Shirin Bruderer, Ivan Ulč, Jasper Dingemanse
BACKGROUND AND OBJECTIVES: Selexipag is an oral, non-prostanoid, selective prostacyclin receptor agonist recently marketed for the treatment of pulmonary arterial hypertension (PAH) in adults. Selexipag may also be an effective treatment in children with PAH. The aim of this study was to compare the pharmacokinetics of selexipag and its active metabolite ACT-333679 following single oral administration of one tablet of 200 µg selexipag (Treatment A) vs. 4 paediatric tablets of 50 µg (Treatment B) in healthy adult male subjects...
June 21, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28624000/aneurysms-of-the-azygos-vein
#2
REVIEW
Maximilian Kreibich, Matthias Siepe, Jochen Grohmann, Gregor Pache, Friedhelm Beyersdorf
OBJECTIVE: Azygos vein aneurysms (AVAs) are uncommon and infrequently diagnosed. When confronted with a patient presenting with an AVA, physicians can rely on only a few case reports after an extensive literature search. To date, no guideline, no rule, and no review on the optimal treatment strategy for these patients exist. METHODS: A PubMed and MEDLINE database search for papers and case reports describing AVA was performed. Cases from our own institutions were also reviewed...
July 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28597780/novel-approach-to-classifying-patients-with-pulmonary-arterial-hypertension-using-cluster-analysis
#3
Kishan S Parikh, Youlan Rao, Tariq Ahmad, Kai Shen, G Michael Felker, Sudarshan Rajagopal
Pulmonary arterial hypertension (PAH) patients have distinct disease courses and responses to treatment, but current diagnostic and treatment schemes provide limited insight. We aimed to see if cluster analysis could distinguish clinical phenotypes in PAH. An unbiased cluster analysis was performed on 17 baseline clinical variables of PAH patients from the FREEDOM-M, FREEDOM-C, and FREEDOM-C2 randomized trials of oral treprostinil versus placebo. Participants were either treatment-naïve (FREEDOM-M) or on background therapy (FREEDOM-C, FREEDOM-C2)...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28597752/withdrawal-of-long-term-epoprostenol-therapy-in-pulmonary-arterial-hypertension-pah
#4
George Calcaianu, Mihaela Calcaianu, Matthieu Canuet, Irina Enache, Romain Kessler
Once initiated for pulmonary arterial hypertension (PAH), epoprostenol treatment usually needs to be delivered for an indefinite duration. It is possible that some participants could be transitioned from epoprostenol to oral therapies. We retrospectively evaluated eight PAH participants transitioned from epoprostenol to PAH oral drugs. The criteria for epoprostenol withdrawal were: (1) persistent improvement of clinic and hemodynamic status; (2) stable dose of epoprostenol for the last three months; and (3) the participant's preference for oral therapy after evaluation of risk-benefit...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28587325/sildenafil-suppresses-the-proliferation-and-enhances-the-apoptosis-of-hemangioma-endothelial-cells
#5
Xiaopo He, Yiran Liu, Kai Li, Aijun Yang, Rui Wang, Shaohua Liu
Treatment of infantile hemangiomas (IH) with propranolol was first reported in 2008. Regressions of lymphatic malformations combined with pulmonary hypertension was first reported in 2012 after three children received treatment with oral sildenafil, which serves as an antagonist of phosphodiesterase isoform-5 (PDE-5). A marked expression of endothelial cells in the cytoplasm of IH tissues was obtained in our previous study. Therefore, the present study hypothesized that the antagonist of PDE-5, sildenafil, may lead to the regression of hemangiomas...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28568509/investigation-and-treatment-for-iron-deficiency-in-heart-failure-the-unmet-need-in-lower-and-middle-income-countries
#6
REVIEW
Abel Makubi, David J Roberts
Frank iron deficiency has been associated with a wide range of cardiac and pulmonary abnormalities including non-ischaemic cardiomyopathy. Iron deficiency anaemia and isolated iron deficiency are well-defined adverse prognostic factors in non-ischaemic cardiac failure. Furthermore, iron-deficient patients in chronic heart failure with a serum ferritin of <100 μg/l or <300 μg/l with reduced transferrin saturation of <20%, who were given intravenous iron showed improved clinical outcomes. Iron deficiency with or without anaemia affects over a quarter of the world's population, but the impact of iron deficiency in heart failure and the effective management of iron deficiency in heart failure in Lower and Middle Income Countries (LMICs) is not well described...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28556581/population-modeling-of-selexipag-pharmacokinetics-and-clinical-response-parameters-in-patients-with-pulmonary-arterial-hypertension
#7
A Krause, M Machacek, D Lott, N Hurst, S Bruderer, J Dingemanse
Selexipag (Uptravi) is an oral selective IP prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension (PAH). The pivotal GRIPHON study was the largest clinical study ever conducted in PAH patients, providing long-term data from 1,156 patients. PAH comedication did not affect exposure to selexipag, while exposure to its active metabolite ACT-333679 was reduced by 30% when taken in combination, clinically not relevant in the context of individual dose up-titration. Using log-linear regression models linking model-predicted steady-state exposure to pharmacodynamics (PD), exposure to selexipag and ACT-333679 showed some statistically significant, albeit not clinically relevant, effects on exercise capacity, laboratory values, and the occurrence of prostacyclin-related adverse events, but not on vital signs or adverse events denoting hemorrhage...
May 27, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28533253/selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#8
Zachary R Noel, Kazuhiko Kido, Tracy E Macaulay
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosing and administration, and place in therapy of selexipag, an orally administered selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension (PAH), are reviewed. SUMMARY: The first-in-class oral prostacyclin IP receptor agonist selexipag (Uptravi, Actelion Pharmaceuticals) was approved by the Food and Drug Administration in December 2015...
May 22, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28524738/selexipag-a-selective-prostacyclin-receptor-agonist-in-pulmonary-arterial-hypertension-a-pharmacology-review
#9
Jesús Honorato Pérez
Pulmonary hypertension is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest. Management of pulmonary arterial hypertension (PAH) includes specific drug therapy with calcium channel blockers in vasoreactive patients, or drugs approved for PAH in non-reactive patients that target the endothelin, nitric-oxide and prostacyclin pathways. Areas covered: The review covers receptor selectivity, pharmacokinetics, pharmacodynamics and adverse effects (AEs) of intravenous (IV) epoprostenol (synthetic prostacyclin); the prostacyclin analogs iloprost, beraprost, and treprostinil administered by IV, subcutaneous, inhaled or oral routes; and the oral selective prostacyclin receptor agonist selexipag...
July 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28523018/effect-of-azithromycin-in-combination-with-simvastatin-in-the-treatment-of-chronic-obstructive-pulmonary-disease-complicated-by-pulmonary-arterial-hypertension
#10
Peidong Wang, Jie Yang, Yanwei Yang, Zhixin Ding
OBJECTIVE: To evaluate the effect of azithromycin in combination with simvastatin in the treatment of chronic obstructive pulmonary disease (COPD) complicated by pulmonary arterial hypertension. METHODS: Eighty-six patients who developed COPD and pulmonary arterial hypertension and received treatment from August 2013 to October 2014 were selected and randomly divided into an observation group and a control group using random number table, 43 in each group. Patients in the control group were orally administrated 20 mg of simvastatin, once a day...
March 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28522783/splenic-abcesses-as-infectious-complication-following-127-implantation-of-left-ventricular-asssist-device-case-report
#11
Sławomir Gajda, Anna M Szczepanik, Grzegorz Religa, Andrzej Misiak, Andrzej B Szczepanik
Left ventricular assist device (LVAD) is one of the modern management therapies in patients with advanced heart failure, and it serves as a bridge to heart transplantation or even as destination therapy. However, it is burdened with a high risk of thromboembolic, hemorrhagic, and infectious complications despite prophylactic management. Splenic abscesses, as septic complications following implantation of mechanical ventricular support, have not yet been described in the literature. We report of a patient with severe left ventricular insufficiency (NYHA II/III), pulmonary hypertension, and arrhythmia who underwent implantation of the Heart Ware® pump for left ventricular support with simultaneous tricuspidvalvoplasty, as a bridge therapy to heart transplantation...
February 28, 2017: Polski Przeglad Chirurgiczny
https://www.readbyqxmd.com/read/28494686/clinical-pharmacology-efficacy-and-safety-of-selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#12
REVIEW
Shirin Bruderer, Noémie Hurst, Tatiana Remenova, Jasper Dingemanse
Selexipag is the first oral, non-prostanoid, selective prostacyclin receptor (IP receptor) agonist, approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients. Areas covered: This article reviews the clinical pharmacology, efficacy, and safety of selexipag in the treatment of PAH. Expert opinion: Selexipag is the first oral drug that selectively targets the prostacyclin pathway, and has evidence of long-term efficacy and safety. In the global phase 3 study GRIPHON (NCT01106014) in PAH patients, selexipag significantly reduced the risk of the primary composite outcome of morbidity/mortality (M/M)...
June 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28476928/selexipag-active-metabolite-act-333679-displays-strong-anticontractile-and-antiremodeling-effects-but-low-%C3%AE-arrestin-recruitment-and-desensitization-potential
#13
John Gatfield, Katalin Menyhart, Daniel Wanner, Carmela Gnerre, Lucile Monnier, Keith Morrison, Patrick Hess, Marc Iglarz, Martine Clozel, Oliver Nayler
Prostacyclin (PGI2) receptor (IP receptor) agonists, which are indicated for the treatment of pulmonary arterial hypertension (PAH), increase cytosolic cAMP levels and thereby inhibit pulmonary vasoconstriction, pulmonary arterial smooth muscle cell (PASMC) proliferation, and extracellular matrix synthesis. Selexipag (Uptravi, 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide) is the first nonprostanoid IP receptor agonist, it is available orally and was recently approved for the treatment of PAH...
July 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28458514/riociguat-a-soluble-guanylate-cyclase-stimulator-for-the-treatment-of-pulmonary-hypertension
#14
REVIEW
Tian-Yu Lian, Xin Jiang, Zhi-Cheng Jing
Despite advances in treatments and improved survival, patients with pulmonary hypertension still experience poor exercise and functional capacity, which has a significant detrimental impact on their quality of life. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine 3',5'-monophosphate (cGMP) pathway has been shown to play an important role in cardiovascular physiology, especially in vasodilation and pulmonary vascular tone. The oral sGC stimulator riociguat has a dual mode of action on the NO-sGC-cGMP pathway: direct stimulation of sGC independent of NO and indirect simulation via sensitization of sGC to endogenous NO...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28422845/response-to-benzodiazepines-and-the-clinical-course-in-malignant-catatonia-associated-with-schizophrenia-a-case-report
#15
Kazutaka Ohi, Aki Kuwata, Takamitsu Shimada, Toshiki Yasuyama, Yusuke Nitta, Takashi Uehara, Yasuhiro Kawasaki
BACKGROUND: Malignant catatonia (MC) is a disorder consisting of catatonic symptoms, hyperthermia, autonomic instability, and altered mental status. Neuroleptic malignant syndrome (NMS) caused by antipsychotics is considered a variant of MC. Benzodiazepine (BZD) medications are safe and effective treatments providing rapid relief from MC. This case study reports a detailed clinical course of a case of MC associated with schizophrenia initially diagnosed as NMS that responded successfully to BZDs but not to dantrolene...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28420826/efficacy-and-safety-of-an-orally-administered-selective-prostacyclin-receptor-agonist-selexipag-in-japanese-patients-with-pulmonary-arterial-hypertension
#16
Nobuhiro Tanabe, Satoshi Ikeda, Nobuhiro Tahara, Keiichi Fukuda, Masaru Hatano, Hiroshi Ito, Tomotaka Nakayama, Toshihisa Anzai, Akiyoshi Hashimoto, Teruo Inoue, Kouji Kajinami, Yasuki Kihara, Hideyuki Kinoshita, Koichiro Kuwahara, Toyoaki Murohara, Osamu Okazaki, Satoshi Sakai, Toru Satoh, Yutaka Takeda, Yasuchika Takeishi, Mitsugu Taniguchi, Hiroshi Watanabe, Takeshi Yamamoto, Keiko Yamauchi-Takihara, Koichiro Yoshioka, Shigetake Sasayama
BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 μg twice daily and titrated up to 1,600 μg by increments of 200 μg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683...
April 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28410199/chronic-intratracheal-application-of-the-soluble-guanylyl-cyclase-stimulator-bay-41-8543-ameliorates-experimental-pulmonary-hypertension
#17
Matthieu Amirjanians, Bakytbek Egemnazarov, Akylbek Sydykov, Baktybek Kojonazarov, Ralf Brandes, Himal Luitel, Kabita Pradhan, Johannes-Peter Stasch, Gorden Redlich, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Hossein Ghofrani, Ralph Schermuly
Dysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP synthesis via sGC are important therapeutic options for treatment of PH patients. An unwanted effect of this novel class of drugs is their systemic hypotensive effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the sGC stimulator BAY41-8543 could diminish its systemic vasodilating effect.Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal delivery was tested in healthy rats...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389079/safety-and-tolerability-of-subcutaneous-treprostinil-in-newborns-with-congenital-diaphragmatic-hernia-and-life-threatening-pulmonary-hypertension
#18
E Carpentier, S Mur, E Aubry, L Pognon, T Rakza, F Flamein, D Sharma, P Tourneux, L Storme
BACKGROUND: Prolonged pulmonary hypertension (PH) is highly predictive for pulmonary morbidity and death in infants with congenital diaphragmatic hernia (CDH). OBJECTIVES: To report the effects and tolerability of subcutaneous treprostinil in newborns with severe CDH and late life-threatening PH. METHODS: We recorded clinical and echocardiography data before and after starting subcutaneous treprostinil, on patients with severe CDH and late PH, refractory to inhaled nitric oxide and oral sildenafil...
March 28, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28337527/phase-ii-study-of-the-c-met-inhibitor-tivantinib-arq-197-in-patients-with-relapsed-or-relapsed-refractory-multiple-myeloma
#19
Muhamed Baljevic, Shadia Zaman, Veerabhadran Baladandayuthapani, Yan Heather Lin, Claudia Morales de Partovi, Zuzana Berkova, Behrang Amini, Sheeba K Thomas, Jatin J Shah, Donna M Weber, Min Fu, Charles S Cleeland, Xin Shelley Wang, Christine M Stellrecht, Richard E Davis, Varsha Gandhi, Robert Z Orlowski
The hepatocyte growth factor/c-MET pathway has been implicated in the pathobiology of multiple myeloma, and c-MET inhibitors induce myeloma cell apoptosis, suggesting that they could be useful clinically. We conducted a phase II study with the c-MET inhibitor tivantinib in patients with relapsed, or relapsed and refractory myeloma whose disease had progressed after one to four prior therapies. Tivantinib, 360 mg orally per dose, was administered twice daily continuously over a 4-week treatment cycle without a cap on the number of allowed cycles, barring undue toxicities or disease progression...
June 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28337251/pentaerythritol-tetranitrate-in-vivo-treatment-improves-oxidative-stress-and-vascular-dysfunction-by-suppression-of-endothelin-1-signaling-in-monocrotaline-induced-pulmonary-hypertension
#20
Sebastian Steven, Matthias Oelze, Moritz Brandt, Elisabeth Ullmann, Swenja Kröller-Schön, Tjebo Heeren, Lan P Tran, Steffen Daub, Mobin Dib, Dirk Stalleicken, Philip Wenzel, Thomas Münzel, Andreas Daiber
Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration...
2017: Oxidative Medicine and Cellular Longevity
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