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Hong-Yu Kuang, Yu-Hao Wu, Qi-Jian Yi, Jie Tian, Chun Wu, We Nian Shou, Tie-Wei Lu
BACKGROUND: Oral bosentan has been widely applied in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). A systemic review and meta-analysis was conducted for a therapeutic evaluation of oral bosentan in both adult and pediatric patients with PAH-CHD. The acute responses and a long-term effect were respectively assessed in a comparison with baseline characteristics, and the improvement of exercise tolerance was analyzed. METHODS: PubMed, Medline, Embase, and Cochrane Central Register of clinical controlled trails or observational studies have been searched for a recording of bosentan effects on the PAH-CHD participants...
March 2018: Medicine (Baltimore)
Hyo-Jung Lee, Hong-Goo Lee, Yong-Bin Kwon, Ju-Young Kim, Yun-Seok Rhee, Jinmann Chon, Eun-Soek Park, Dong-Wook Kim, Chun-Woong Park
In this study, we prepared carrier-based formulations for dry powder inhalers by mixing bosentan microparticles with carrier, prepared in three separate types of lactose. Spray-dried, milled and sieved lactose resulted in formulations with various shapes, surface morphology and particle size distributions. In the spray-dried lactose, the micronized bosentan particles were trapped and strongly interlocked in the rugged surface of spray-dried lactose, whereas in the milled and sieved lactose they exhibited lower binding affinity onto the smooth surface of carrier...
March 3, 2018: European Journal of Pharmaceutical Sciences
Masanobu Sato, Kota Toshimoto, Atsuko Tomaru, Takashi Yoshikado, Yuta Tanaka, Akihiro Hisaka, Wooin Lee, Yuichi Sugiyama
Bosentan is a substrate of hepatic uptake transporter organic anion transporting polypeptides (OATPs), and undergoes extensive hepatic metabolism by cytochrome P450 (CYPs), namely, CYP3A4 and CYP2C9. Several clinical investigations have reported a nonlinear relationship between bosentan doses and its systemic exposure, which likely involves the saturation of OATP-mediated uptake, CYP-mediated metabolism, or both in the liver. Yet, the underlying causes for the nonlinear bosentan pharmacokinetics are not fully delineated...
February 23, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Jennifer Ryan, Ryan E Morgan, Yuan Chen, Laurie Volak, Robert T Dunn, Kenneth W Dunn
The bile salt export pump (BSEP) is expressed at the canalicular domain of hepatocytes, where it mediates the elimination of monovalent bile salts into the bile. Inhibition of BSEP is considered a susceptibility factor for drug-induced liver injury (DILI) that often goes undetected during non-clinical testing. Although in vitro assays exist for screening BSEP inhibition, a reliable and specific method for confirming Bsep inhibition in vivo would be a valuable follow-up to a BSEP screening strategy, helping to put a translatable context around in vitro inhibition data, incorporating processes such as metabolism, protein binding, and other exposure properties that are lacking in most in vitro BSEP models...
February 21, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Christian Apitz, Dietmar Schranz
No abstract text is available yet for this article.
February 16, 2018: Respiration; International Review of Thoracic Diseases
Laxminarayan Bhat, Jon Hawkinson, Marc Cantillon, Dasharatha G Reddy, Seema R Bhat, Charles-E Laurent, Annie Bouchard, Marzena Biernat, Dany Salvail
Pulmonary arterial hypertension (PAH), a condition that is defined by pulmonary vasculature constriction and remodeling, involves dysfunctional signaling of the serotonin (5-HT) receptors, 5-HT 2/2B/7 . In a rat model of monocrotaline (MCT)-induced PAH, the effectiveness of RP5063 (RP), a dopamine and 5-HT receptor modulator, was evaluated as monotherapy and as an adjunct to standard PAH treatments. After a single 60mg/kg dose of MCT, rats received vehicle (MCT+Veh; gavage twice-daily [b.i.d.]), RP (10mg/kg; gavage b...
February 14, 2018: European Journal of Pharmacology
Nika Skoro-Sajer, Christian Gerges, Olga Hajnalka Balint, Dora Kohalmi, Monika Kaldararova, Iveta Simkova, Johannes Jakowitsch, Harald Gabriel, Helmut Baumgartner, Mario Gerges, Roela Sadushi-Kolici, David S Celermajer, Irene Marthe Lang
OBJECTIVE: To assess the efficacy and safety of subcutaneous treprostinil in adult patients with congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after 12 months of treatment. METHODS: Consecutive adult patients with CHD-PAH received subcutaneous treprostinil to maximum tolerated doses in an observational study. RESULTS: Advanced CHD-PAH patients with WHO class III or IV disease (n=32, age 40±10 years, 20 females) received treprostinil for suboptimal response to bosentan (n=12), WHO functional class IV disease (FC, n=7) or prior to bosentan approval (n=13)...
February 7, 2018: Heart: Official Journal of the British Cardiac Society
Peter Afdal, Antoine F AbdelMassih
Severe angio-obliterative pulmonary vascular disease (PAH) remains a disease characterized by great morbidity and shortened survival. Unfortunately, the only currently available treatments for angio-obliterative changes are palliative in the form of pulmonary vasodilators evolving from the phosphodiesterase inhibitor sildenafil to endothelin receptor antagonist: Bosentan; while the only definitive treatment is lung transplantation which remains dependent on the availability of donors and the transplant policies which vary widely from a country to another...
February 12, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Ulrike S Kraemer, Lisette Leeuwen, Thomas B Krasemann, René M H Wijnen, Dick Tibboel, Hanneke IJsselstijn
OBJECTIVES: Pulmonary hypertension is one of the main causes of mortality and morbidity in patients with congenital diaphragmatic hernia. Currently, it is unknown whether pulmonary hypertension persists or recurs during the first year of life. DESIGN: Prospective longitudinal follow-up study. SETTING: Tertiary university hospital. PATIENTS: Fifty-two congenital diaphragmatic hernia patients admitted between 2010 and 2014...
February 6, 2018: Pediatric Critical Care Medicine
Xinwang Chen, Zhenguo Zhai, Ke Huang, Wanmu Xie, Jun Wan, Chen Wang
BACKGROUND AND OBJECTIVE: Bosentan therapy has been recommended for pulmonary arterial hypertension (PAH) and might be beneficial for chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to evaluate the specific effects of bosentan for PAH and CTEPH. MATERIALS AND METHODS: We performed a systemic review and meta-analysis of randomized controlled trials (RCTs), comparing efficacy and safety of bosentan treatment for PAH and CTEPH through major biomedical database...
February 2, 2018: Clinical Respiratory Journal
Andrea Combalia, Priscila Giavedoni, Lorena Tamez, Josep M Grau-Junyent, Jose M Mascaró
No abstract text is available yet for this article.
January 17, 2018: JAMA Dermatology
Daniel L Varela, Mohamed Teleb, Wael El-Mallah
Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD) is the third most common cause of PAH, and it is becoming increasingly common as improvements in the management of CHD have led to increased life expectancy for these patients. The medical management of PAH due to CHD (PAH-CHD) is largely the same as what has been used for the treatment of idiopathic PAH, though the body of literature supporting this management decision is very small. There are currently few studies available which specifically focus on the treatment of PAH-CHD...
2018: Open Heart
Q Liu, C Zhang, Q Q Li, Y Zhu, D Zhang, W G Zhao, H Gu
Objective: To analyze the prognosis and associated risk factors of pediatric idiopathic pulmonary arterial hypertension. Methods: A total of 119 patients under 18 years of age diagnosed as idiopathic pulmonary arterial hypertension in the Pulmonary Arterial Hypertension Center in Beijing Anzhen Hospital between June 2007 and May 2017 were enrolled in this retrospective study. The clinical informations and follow-up data were collected. The endpoints of follow-up were defined as death or undergoing lung transplantation...
January 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
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
Rui Li, Emi Kimoto, Mark Niosi, David A Tess, Jian Lin, Larry M Tremaine, Li Di
Predicting human pharmacokinetics of novel compounds is a critical step in drug discovery and clinical study design, but continues to be a challenging task for hepatic transporter substrates, particularly in predicting their liver exposures. In this study, using bosentan as an example, we have prospectively predicted systemic exposure and (pseudo) steady state unbound liver-to-unbound plasma ratio (Kpuu) in healthy subjects using (1) a mechanistic approach solely based on in vitro hepatocyte assays, and (2) an approach based on hepatic process rates from monkey in vivo data but Michaelis-Menten constants from in vitro data...
January 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Rui Li, Mark Niosi, Nathaniel Johnson, David A Tess, Emi Kimoto, Jian Lin, Xin Yang, Keith A Riccardi, Sangwoo Ryu, Ayman F El-Kattan, Tristan S Maurer, Larry M Tremaine, Li Di
Understanding liver exposure of hepatic transporter substrates in clinical studies is often critical as it typically governs pharmacodynamics, drug-drug interactions, and toxicity for certain drugs. However, this is a challenging task since there is currently no easy method to directly measure drug concentration in the human liver. Using bosentan as an example, a new approach has been demonstrated to estimate liver exposure based on observed systemic pharmacokinetics from clinical studies using physiologically-based pharmacokinetic modeling...
January 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Maxime Fouchard, Brigitte Pan Petesch, Claire Abasq-Thomas, Alain Saraux, Laurent Misery, Emilie Brenaut
We report the observation of a 57-year-old patient followed for an Erasmus syndrome (a systemic sclerosis developing secondary to silica exposure) (1) diagnosed in 2002 after being exposed as a dental technician, for whom a severe thrombocytopenia was discovered. He suffered from a pulmonary fibrosis, polyarthralgia, esophageal dysphagia and cutaneous involvement such as finger ulcerations and sclerodactylia. The treatment was made of nifedipine 30mg/day, esomeprazole 20mg/day and bosentan 25 mg twice a day...
January 5, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Thao T Tran, Allen D Brinker, Monica Muñoz
Several endothelin receptor antagonists (ERAs) that were developed for the treatment of pulmonary arterial hypertension (PAH), including bosentan and sitaxentan, have been linked to clinically significant hepatocellular injury, as well as liver failure. We describe the first case of fulminant hepatitis to be reported in association with the ERA macitentan. This case was recently identified within the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and and describes liver transplantation occuring 13 months following macitentan initiation in a young patient (23-years old) with idiopathic PAH New York Heart Association (NYHA) functional class III...
December 29, 2017: Pharmacotherapy
B Aranegui, J Jiménez-Reyes
Morphea is an inflammatory, fibrosing skin disorder. When it occurs in childhood, it is also known as localized juvenile scleroderma. It is more common in girls and typically appears around the age of 5 to 7 years. According to a recent classification system, morphea is divided into 5 types: circumscribed (plaque), linear, generalized, pansclerotic, and mixed. Approximately 40% of patients present extracutaneous manifestations. Childhood morphea is treated with phototherapy, oral or topical calcitriol, topical tacrolimus 0...
December 13, 2017: Actas Dermo-sifiliográficas
Yosuke Tanaka, Mitsunori Hino, Akihiko Gemma
BACKGROUND: No drugs have been approved for the treatment of patients with pulmonary hypertension (PH) secondary to idiopathic pulmonary fibrosis (IPF), particularly those with idiopathic honeycomb lung. This study was conducted to investigate the long-term efficacy and safety of bosentan for PH based on changes in prognosis and respiratory failure. METHODS: IPF patients with borderline or less severe PH and completely organized honeycomb lung were randomized (1:1) to bosentan or no treatment for PH for 2 years and assessed at baseline and every 6 months for respiratory failure, activities of daily living (ADL), lung and heart functions by right cardiac catheterization, and other parameters...
December 13, 2017: BMC Pulmonary Medicine
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