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https://www.readbyqxmd.com/read/29792287/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-glpg1690-a-novel-autotaxin-inhibitor-to-treat-idiopathic-pulmonary-fibrosis-flora-a-phase-2a-randomised-placebo-controlled-trial
#1
Toby M Maher, Ellen M van der Aar, Olivier Van de Steen, Lisa Allamassey, Julie Desrivot, Sonia Dupont, Liesbeth Fagard, Paul Ford, Ann Fieuw, Wim Wuyts
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. People with IPF have increased concentrations of autotaxin in lung tissue and lysophosphatidic acid (LPA) in bronchoalveolar lavage fluid and exhaled condensate. GLPG1690 (Galapagos, Mechelen, Belgium) is a novel, potent, selective autotaxin inhibitor with good oral exposure. We explored the effects of GLPG1690 in patients with IPF. METHODS: This was a randomised, double-blind, placebo-controlled phase 2a study done in 17 centres in Italy, Ukraine and the UK...
May 18, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29790019/development-of-a-topical-48-h-release-formulation-as-an-anti-scarring-treatment-for-deep-partial-thickness-burns
#2
Rossella Dorati, Jorge L Medina, Patrick P DeLuca, Kai P Leung
The purpose of this study was to develop pirfenidone (PF) ointment formulations for a dose finding study in the prophylactic treatment of deep partial-thickness burns in a mouse model. A preformulation study was performed to evaluate the solubility of PF in buffers and different solvents and its stability. Three different formulations containing 1, 3.5, and 6.5% w/w PF were prepared and optimized for their composition for testing in mice. Optimized formulations showed promising in vitro release profiles, in which 20-45% of PF was released in the first 7 h and 70-90% released within 48 h...
May 11, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29785264/delay-and-inequalities-in-the-treatment-of-idiopathic-pulmonary-fibrosis-the-case-of-two-nordic-countries
#3
Ida Pesonen, Lisa Carlson, Nicola Murgia, Riitta Kaarteenaho, Carl Magnus Sköld, Marjukka Myllärniemi, Giovanni Ferrara
Background: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive loss of lung function with high mortality within the first 5 years from diagnosis. In 2011-2014, two drugs, pirfenidone and nintedanib, have been approved worldwide for prevention of IPF progression. National IPF-registries have been established in both Finland and Sweden. Our study explored potential differences in the care of IPF in these two countries. Methods: Patients included consecutively in the Finnish and Swedish IPF-registries from January 1, 2014 through December 31, 2016 were included in the study...
2018: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/29783158/pirfenidone-ameliorates-lipopolysaccharide-induced-pulmonary-inflammation-and-fibrosis-by-blocking-nlrp3-inflammasome-activation
#4
Yi Li, Haitao Li, Shuai Liu, Pinhua Pan, Xiaoli Su, Hongyi Tan, Dongdong Wu, Lemeng Zhang, Chao Song, Minhui Dai, Qian Li, Zhi Mao, Yuan Long, Yongbin Hu, Chengping Hu
Acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by its acute onset, diffuse alveolar damage, intractable hypoxemia, and non-cardiogenic pulmonary edema. Acute lung injury(ALI) can trigger persistent lung inflammation and fibrosis through activation of the NLRP3 inflammasome and subsequent secretion of mature IL-1β, suggesting that the NLRP3 inflammasome is a potential therapeutic target for ALI, for which new therapeutic approaches are needed. Our present study aims to assess whether pirfenidone,with anti-fibrotic and anti-inflammatory properties, can improve LPS-induced inflammation and fibrosis by inhibiting NLRP3 inflammasome activation...
May 18, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29780123/the-efficacy-and-safety-of-long-term-pirfenidone-therapy-in-patients-with-idiopathic-pulmonary-fibrosis
#5
Kazumasa Ogawa, Atsushi Miyamoto, Shigeo Hanada, Yui Takahashi, Kyoko Murase, Sayaka Mochizuki, Hironori Uruga, Hisashi Takaya, Nasa Morokawa, Kazuma Kishi
Objective Pirfenidone (PFD) is often used for years, but the efficacy and safety of long-term PFD therapy in patients with idiopathic pulmonary fibrosis (IPF) are not fully understood. Methods and Patients We retrospectively evaluated 46 patients with IPF who received PFD between February 2009 and August 2014. The efficacy and safety of PFD therapy were compared between 2 groups: long-term therapy patients who received PFD for over 1 year (group L, n=30, 65%) and short-term therapy patients who could not receive PFD for more than 1 year due to worsening of their condition or side effects (group S, n=16, 35%)...
May 18, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29767392/a-novel-rabbit-model-for-benign-biliary-stricture-formation-and-the-effects-of-medication-infusions-on-stricture-formation
#6
Qin Yang, Junke Wang, Fei Liu, Wenjie Ma, Haijie Hu, Congdun Ran, Fuyu Li, Qiuwei Pan
BACKGROUND: Benign biliary stricture (BBS) is highly refractory. Currently, there is no effective strategy for prevention of BBS recurrence. The aim of this study is to establish a novel BBS rabbit model and to investigate the efficacy of biliary infusion with anti-proliferative medications for treating BBS. METHOD: A BBS model was established via surgical injury and biliary infection. The biliary infusion tube was inserted into the common bile duct via the stump of cystic duct after cholecystectomy...
May 16, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29747274/-real-life-experience-with-pirfenidone-in-idiopathic-pulmonary-fibrosis
#7
Y J Yan, Y L Fan, S W Yu, Q Ye
Objective: To evaluate the efficacy and safety of pirfenidone (PFD) in idiopathic pulmonary fibrosis (IPF) in real-life world. Methods: 47 consecutive patients with IPF taking PFD for at least 12 months (PFD group) were included for analysis, with 47 patients with IPF who did not take PFD as controls. Data were collected from clinical charts to evaluate the lung function parameters and the adverse reactions of PFD. Results: In the PFD group, the percent predicted forced vital capacity (FVC%) and diffusing capacity of carbon monoxide (D(L)CO%) increased by (3...
May 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29724385/sildenafil-added-to-pirfenidone-in-patients-with-advanced-idiopathic-pulmonary-fibrosis-and-risk-of-pulmonary-hypertension-a-phase-iib-randomised-double-blind-placebo-controlled-study-rationale-and-study-design
#8
Jürgen Behr, Steven D Nathan, Sergio Harari, Wim Wuyts, Klaus-Uwe Kirchgaessler, Monica Bengus, Frank Gilberg, Athol U Wells
BACKGROUND: Pulmonary hypertension (PH) is commonly observed in patients with advanced idiopathic pulmonary fibrosis (IPF). Despite the availability of therapies for both IPF and PH, none are approved for PH treatment in the context of significant pulmonary disease. This study will investigate the use of sildenafil added to pirfenidone in patients with advanced IPF and risk of PH, who represent a group with a high unmet medical need. METHODS: This Phase IIb, randomised, double-blind, placebo-controlled trial is actively enrolling patients and will study the efficacy, safety and tolerability of sildenafil or placebo in patients with advanced IPF and intermediate or high probability of Group 3 PH who are receiving a stable dose of pirfenidone...
May 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29718783/an-update-on-emerging-drugs-for-the-treatment-of-idiopathic-pulmonary-fibrosis
#9
Shambhu Aryal, Steven D Nathan
Idiopathic pulmonary fibrosis is a chronic, progressive fibrotic lung disease of unknown etiology associated with a high morbidity and mortality. The hallmark of the disease is impaired healing after alveolar epithelial injury in the setting of a genetic predisposition. Development of two new drugs has changed the landscape of the treatment of IPF but more work is needed to improve outcomes and improve survival. Areas covered: The development of two antifibrotic agents, nintedanib and pirfenidone has been an exciting landmark in the treatment of IPF...
May 8, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29715556/chitosan-alginate-nano-carrier-for-transdermal-delivery-of-pirfenidone-in-idiopathic-pulmonary-fibrosis
#10
Marzieh Abnoos, Mojdeh Mohseni, Seyed Ali Javad Mousavi, Khadijeh Ashtari, Roya Ilka, Bita Mehravi
Pirfenidone (PFD) is one of the pyridine family components with anti-inflammatory, antifibrotic effects and US FDA approved for the treatment of idiopathic pulmonary fibrosis (IPF). Presently, PFD is administered orally and this has setbacks. Hence, it is important to eliminate the pharmacotherapeutic limitations of PFD. This research was carried out to study the possibility of transdermal delivery of PFD using chitosan-sodium alginate nanogel carriers. In order to synthesize chitosan-sodium alginate nanoparticles loaded with PFD, the pre-gelation method was used...
April 28, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29703175/anti-fibrotic-effects-of-pirfenidone-and-rapamycin-in-primary-ipf-fibroblasts-and-human-alveolar-epithelial-cells
#11
M Molina-Molina, C Machahua-Huamani, V Vicens-Zygmunt, R Llatjós, I Escobar, E Sala-Llinas, P Luburich-Hernaiz, J Dorca, A Montes-Worboys
BACKGROUND: Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone. METHODS: Primary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor β1 (TGF-β)...
April 27, 2018: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29702057/undifferentiated-pleomorphic-sarcoma-after-pirfenidone-use-a-case-report
#12
Christine A Moore, Aaysha Kapila
INTRODUCTION: Pirfenidone was approved in 2014 for the treatment of idiopathic pulmonary fibrosis. Pirfenidone inhibits several factors such as tissue growth factor-β and platelet-derived growth factor, leading to decreased epithelial and fibroblast proliferation and collagen synthesis. The drug improves progression-free survival and is well tolerated, with minimal side effects. However, data on its long-term effects are lacking. CASE PRESENTATION: We present a rare case in which an undifferentiated pleomorphic sarcoma developed in a 59-year-old man with idiopathic pulmonary fibrosis who was treated with pirfenidone for more than a year...
April 4, 2018: Permanente Journal
https://www.readbyqxmd.com/read/29660469/dothiorelone-derivatives-from-an-endophyte-diaporthe-pseudomangiferaea-inhibit-the-activation-of-human-lung-fibroblasts-mrc-5-cells
#13
Zhen Liu, Jingyi Zhao, Xiao Liang, Xiaoxi Lv, Yong Li, Jing Qu, Yunbao Liu
Nine new compounds (1-6 and 16-18) and nine known compounds (7-15) were isolated from the Diaporthe pseudomangiferaea, an endophytic fungus obtained from the leaves of the toxic Chinese folk medicine Tylophora ouata. Their structures were elucidated by NMR spectroscopy and MS spectrometry analyses. The absolute configurations were established according to the specific rotation or electron circular dichroism method. Compounds 1, 4, 9, 11, 14 and 15 inhibited the TFG-β induced activation of human lung fibroblasts MRC-5 cells by 17...
April 13, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29621494/pirfenidone-inhibits-cryoablation-induced-local-macrophage-infiltration-along-with-its-associated-tgfb1-expression-and-serum-cytokine-level-in-a-mouse-model
#14
Yangkui Gu, Govindarajan Srimathveeravalli, Liqun Cai, Eisuke Ueshima, Majid Maybody, Hooman Yarmohammadi, Yuan-Shan Zhu, Jeremy C Durack, Stephen B Solomon, Jonathan A Coleman, Joseph P Erinjeri
PURPOSE: To investigate the effects of pirfenidone (PFD) on post-cryoablation inflammation in a mouse model. MATERIALS AND METHODS: In this IACUC-approved study, eighty Balb/c mice were randomly divided into four groups (20/group): sham + vehicle, sham + PFD, cryoablation + vehicle, and cryoablation + PFD. For cryoablation groups, a 20% freeze rate cryoablation (20 s to less than -100 °C) was used to ablate normal muscle in the right flank. For sham groups, the cryoprobe was advanced into the flank and maintained for 20 s without ablation...
April 2, 2018: Cryobiology
https://www.readbyqxmd.com/read/29601564/-nintedanib-in-the-treatment-of-fibrosing-interstital-lung-diseases
#15
REVIEW
Katarzyna Lewandowska
Nintedanib is an intracellular tyrosine kinase inhibitor approved in a treatment of idiopathic pulmonary fibrosis. It reduces the annual rate of forced vital capacity decline by approximately 50%, that results in slowing of disease progression. The drug also reduces the incidence of acute exacerbations of idiopathic pulmonary fibrosis. The efficacy of nintedanib was the same in different groups of patients, irrespectively to disease status, age, gender and race. The most frequent side effects were gastrointestinal, i...
March 27, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29601563/-advances-in-differential-diagnosis-and-treatment-of-patients-with-sarcoidosis
#16
REVIEW
Tadeusz Płusa
The implementation of treatment in patients with sarcoidosis (SA) must be associated with the certainty of diagnosis, which is difficult due to the lack of unambiguous criteria. Finding the presence of noncaseating granulomas in bioptic material is not always indicative of SA. The main point of SA's diagnosis is the level of its activity, because only patients in the active stage should be qualified for treatment. In therapy, glucocorticosteroids or second-line drugs - methotrexate or azathioprine are still recommended...
March 27, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29587263/a-real-life-multicenter-national-study-on-nintedanib-in-severe-idiopathic-pulmonary-fibrosis
#17
Sergio Harari, Antonella Caminati, Venerino Poletti, Marco Confalonieri, Stefano Gasparini, Donato Lacedonia, Fabrizio Luppi, Alberto Pesci, Alfredo Sebastiani, Paolo Spagnolo, Carlo Vancheri, Elisabetta Balestro, Martina Bonifazi, Stefania Cerri, Federica De Giacomi, Rossana Della Porta, Maria Pia Foschino Barbaro, Annalisa Fui, Patrizio Pasquinelli, Roberta Rosso, Sara Tomassetti, Claudia Specchia, Paola Rottoli
BACKGROUND: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. OBJECTIVES: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. METHODS: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib...
March 27, 2018: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29572333/risk-of-clinically-relevant-pharmacokinetic-based-drug-drug-interactions-with-drugs-approved-by-the-u-s-food-and-drug-administration-between-2013-and-2016
#18
Jingjing Yu, Zhu Zhou, Jessica Tay-Sontheimer, Rene H Levy, Isabelle Ragueneau-Majlessi
A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database and the clinical relevance of these observations was characterized based on information from New Drug Application reviews. CYP3A was identified as a major contributor to clinical drug-drug interactions (DDIs), involved in approximately 2/3 of all interactions. Transporters (alone or with enzymes) were found to participate in about half of all interactions, although most of these were weak-to-moderate interactions...
March 23, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29561855/accumulation-of-mechanical-forces-in-tumors-is-related-to-hyaluronan-content-and-tissue-stiffness
#19
Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Hyaluronan is abundant in the extracellular matrix of many desmoplastic tumors and determines in large part the tumor biochemical and mechanical microenvironment. Additionally, it has been identified as one of the major physiological barriers to the effective delivery of drugs to solid tumors and its targeting with the use of pharmaceutical agents has shown to decompress tumor blood vessels, and thus improve tumor perfusion and efficacy of cytotoxic drugs. In this study, we investigated the contribution of hyaluronan to the accumulation of mechanical forces in tumors...
2018: PloS One
https://www.readbyqxmd.com/read/29552620/activation-of-myofibroblast-trpa1-by-steroids-and-pirfenidone-ameliorates-fibrosis-in-experimental-crohn-s-disease
#20
Lin Hai Kurahara, Keizo Hiraishi, Yaopeng Hu, Kaori Koga, Miki Onitsuka, Mayumi Doi, Kunihiko Aoyagi, Hidetoshi Takedatsu, Daibo Kojima, Yoshitaka Fujihara, Yuwen Jian, Ryuji Inoue
Background & Aims: The transient receptor potential ankyrin 1 (TRPA1) channel is highly expressed in the intestinal lamina propria, but its contribution to gut physiology/pathophysiology is unclear. Here, we evaluated the function of myofibroblast TRPA1 channels in intestinal remodeling. Methods: An intestinal myofibroblast cell line (InMyoFibs) was stimulated by transforming growth factor-β1 to induce in vitro fibrosis. Trpa1 knockout mice were generated using the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
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