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Benzbromarone

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https://www.readbyqxmd.com/read/29285235/eyes-absent-gene-eya1-is-a-pathogenic-driver-and-a-therapeutic-target-for-melanoma
#1
Joshua Jiawei Zhou, Yuanshen Huang, Xue Zhang, Yabin Cheng, Liren Tang, Xiaodong Ma
EYA1 is a DNA repair enzyme that is induced after DNA damage and is upregulated in melanoma. However, its role in pathogenesis and therapeutic targeting of melanoma is unknown. Our objectives are (1) to study the relationship between EYA1 expression levels and melanoma patients' clinical pathologic parameters including survival; (2) to investigate its impact on cultured melanoma cells in vitro; and (3) to evaluate EYA1 inhibitors' potential as a treatment of melanoma. Melanoma tissue microarrays were used to assess EYA1 protein expression in 326 melanoma tissues, and to correlate the expression with patients' clinical pathological parameters...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29251581/efficacy-and-safety-of-febuxostat-in-kidney-transplant-patients
#2
Chung Hee Baek, Hyosang Kim, Won Seok Yang, Duck Jong Han, Su-Kil Park
OBJECTIVES: Febuxostat, a nonpurine xanthine oxidase, is known to be effective and safe, even in patients with chronic kidney disease. However, there are insufficient data about the efficacy and safety of febuxostat in kidney transplant patients. MATERIALS AND METHODS: We reviewed medical records of all kidney transplant patients who were prescribed febuxostat between August 2012 and May 2015 at Asan Medical Center in Seoul, Korea. The efficacy and safety results of febuxostat in transplant patients were evaluated...
December 18, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29204974/effects-of-discontinuation-of-urate-lowering-therapy-a-systematic-review
#3
Virginie Beslon, Perrine Moreau, Annabel Maruani, Hubert Maisonneuve, Bruno Giraudeau, Jean-Pascal Fournier
BACKGROUND: Urate-lowering therapy (ULT) is associated with low rates of adherence, leading to a potential risk of relapse of gouty arthritis, tophi, or urolithiasis. Our main aim was to identify the recurrence of gouty arthritis, tophi, or urolithiasis after discontinuation of ULT. Secondary aims included an assessment of ULT reintroduction rates and factors associated with relapse. METHODS: We conducted a systematic literature review of clinical studies investigating the effect of discontinuing any ULT (allopurinol, febuxostat, probenecid, sulfinpyrazone, benzbromarone) in adults on long-term therapy...
December 4, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29165620/comparative-effectiveness-of-allopurinol-febuxostat-and-benzbromarone-on-renal-function-in-chronic-kidney-disease-patients-with-hyperuricemia-a-13-year-inception-cohort-study
#4
Hsu-Wen Chou, Hsien-Tsai Chiu, Ching-Wei Tsai, I-Wen Ting, Hung-Chieh Yeh, Han-Chun Huang, Chin-Chi Kuo
Background: Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods: We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis...
November 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29123379/guideline-development-for-the-management-of-gout-role-of-combination-therapy-with-a-focus-on-lesinurad
#5
REVIEW
Graeme Jones, Elena Panova, Richard Day
The aim of this review was to summarize the evidence for combination therapy to achieve serum urate (SUA) target levels in gout. Within this overarching aim, a second aim was to evaluate the evidence for a new uricosuric agent lesinurad, which inhibits urate transport in the kidney. In summary, this review indicates that there are a number of ways to approach patients who do not achieve a target serum urate with allopurinol (APL) monotherapy. These include higher doses of APL up to 600-800 mg/d, switching to febuxostat, or adding in a uricosuric...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29100760/comparative-study-on-the-interaction-between-3-cyp2c9-allelic-isoforms-and-benzbromarone-by-using-lc-ms-ms-method
#6
Lingli He, Chuan Li, Xuyuan Liu, Qingqing Yang, Haizhi Zhang, Weiren Xu, Luyong Zhang, Changxiao Liu
Benzbromarone is a uricosuric drug metabolized predominantly by cytochrome P450 2C9 from in vitro findings. Human CYP2C9 exhibits extensive genetic polymorphism and numbers of clinic studies have demonstrated that CYP2C9 genetic polymorphism has a significant influence on the pharmacokinetics of benzbromarone. But in vitro study on the interaction between CYP2C9 allelic isoforms and benzbromarone was rare. Here, an LC-MS/MS method was established and validated to determine the concentration of benzbromarone in different CYP2C9 enzyme incubation systems for the drug-enzyme interaction study...
October 31, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29021351/metabolic-epoxidation-is-a-critical-step-for-the-development-of-benzbromarone-induced-hepatotoxicity
#7
Hui Wang, Ying Peng, Tingjian Zhang, Qunsheng Lan, Huimin Zhao, Wenbao Wang, Yufei Zhao, Xu Wang, Jianxin Pang, Shaojie Wang, Jiang Zheng
Benzbromarone (BBR) is effective in the treatment of gout; however, clinical findings have shown it can also cause fatal hepatic failure. Our early studies demonstrated that CYP3A catalyzed the biotransformation of BBR to epoxide intermediate(s) that reacted with sulfur nucleophiles of protein to form protein covalent binding both in vitro and in vivo. The present study attempted to define the correlation between metabolic epoxidation and hepatotoxicity of BBR by manipulating the structure of BBR. We rationally designed and synthesized three halogenated BBR derivatives, fluorinated BBR (6-F-BBR), chlorinated BBR (6-Cl-BBR), and brominated BBR (6-Br-BBR), to decrease the potential for cytochrome P450-mediated metabolic activation...
December 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28994541/-effect-of-chinese-herb-chicory-extract-on-expression-of-renal-transporter-glut9-in-rats-with-hyperuricemia
#8
Yu Wang, Zhi-Jian Lin, An-Zheng Nie, Li-Yu Li, Bing Zhang
Sixty SD male rats were randomly divided into normal group, model group, benzbromarone group(20 mg•kg⁻¹•d⁻¹), chicory extract high dose, middle dose and low dose groups (5, 7.5, 10 g•kg⁻¹•d⁻¹). The rats in normal group were given with water, and the rats in other groups were given with 10% fructose solution to establish hyperuricemia models. All the rats were sacrificed on the 42th day. Then their serum uric acid(SUA), serum creatinine(CRE), urea nitrogen(BUN) and urinary uric acid(UUA) levels were detected to calculate the clearance rate of uric acid in kidney(CUA)...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28974978/can-allopurinol-improve-retinopathy-in-diabetic-rats-oxidative-stress-or-uric-acid-which-one-is-the-culprit
#9
Mohsen Goharinia, Athar Zareei, Mansour Rahimi, Hossein Mirkhani
Allopurinol, an inhibitor of xanthine oxidase, reduces both plasma uric acid and oxidative stress and shows useful effects on some complications of diabetes. However, it is not defined which of the above mentioned properties are involved. Moreover, to the best of our knowledge no study has been done on the effects of allopurinol on diabetic retinopathy. In the present study, the effect of allopurinol on experimental diabetic retinopathy and its possible mechanism has been investigated. Thirty two rats were divided into four groups of eight rats each; (1) normal, (2) diabetic control, (3) diabetic + allopurinol (50 mg/kg...
October 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28828541/role-of-the-oatp-transporter-family-and-a-benzbromarone-sensitiveefflux-transporter-in-the-hepatocellular-disposition-of-vincristine
#10
Johan Nicolaï, Louise Thevelin, Qi Bing, Bruno Stieger, Hugues Chanteux, Patrick Augustijns, Pieter Annaert
PURPOSE: Vincristine is known to interfere with OATP-mediated uptake of other compounds, hinting that vincristine itself could be a substrate of OATP transporters. The present study therefore aimed to investigate the role of OATP transporters in the hepatocellular disposition of vincristine. METHODS: Vincristine uptake was studied in suspended rat and human hepatocytes as well as OATP-transfected Chinese hamster ovary (CHO) cells in the absence and presence of OATP transporter inhibitors...
November 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28658988/updates-on-the-treatment-of-gout-including-a-review-of-updated-treatment-guidelines-and-use-of-small-molecule-therapies-for-difficult-to-treat-gout-and-gout-flares
#11
REVIEW
Rose Soskind, Daniel T Abazia, Mary Barna Bridgeman
Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues. Areas covered: In this article, we describe the role of currently available drug therapies for managing acute gout flares and used in reducing serum urate levels. Further, we explore the role of novel small molecular therapies and biologic agents in the treatment of refractory or severe gout symptoms. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-June 2017) was conducted utilizing the key words 'gout', 'interleukin-1 inhibitors', 'acute gout', 'gout treatment', 'urate lowering therapies', 'hyperuricemia', 'colchicine', 'pegloticase', 'lesinurad', 'xanthine oxidase', 'xanthine oxidase inhibitors', 'allopurinol', 'febuxostat', 'uricosurics', 'probenecid', and 'benzbromarone'...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28598529/association-of-a-reactive-intermediate-derived-from-1-6-dihydroxy-metabolite-with-benzbromarone-induced-hepatotoxicity
#12
Mina Yoshida, Naoki Cho, Hidetaka Akita, Kaoru Kobayashi
Treatment with benzbromarone can be associated with liver injury, but the detailed mechanism remains unknown. Our recent studies demonstrated that benzbromarone was metabolized to 1',6-dihydroxybenzbromarone and followed by formation of reactive intermediates that were trapped by glutathione, suggesting that the reactive intermediates may be responsible for the liver injury. The aim of this study was to clarify whether the reactive intermediates derived from 1',6-dihydroxybenzbromarone is a risk factor of liver injury in mice...
June 9, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28544467/a-survey-on-the-beliefs-and-knowledge-of-gout-management-in-new-medical-graduates-new-south-wales-australia
#13
Matthew Terrill, John Riordan
AIM: To assess the beliefs and knowledge of gout management in new medical graduates. METHOD: A survey on gout management was sent to new medical graduates during their orientation week, New South Wales, Australia. RESULTS: Of 15 hospital networks, 11 agreed to participate. From these, 168 graduates responded (23.7% response rate). Most (81.1%) felt that gout was a serious disease, 51.2% answered that they had been taught adequately to manage acute gout, only 37...
May 25, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28539294/-effects-of-clostridium-butyricum-on-serum-uric-acid-and-inflammatory-mediators-in-rats-with-hyperuricemia
#14
Li Wang, Zhi-Rong Fang, Ya-Ting Shen, Yan-Bo Liu, Li-Li Liu
OBJECTIVE: To investigate the effects of intragastric administration of Clostridium butyricum in regulating serum uric acid, lipopolysaccharides (LPS), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rats with hyperuricemia rats. METHODS: Forty SD rats were randomized into 4 equal groups, namely the normal control group, hyperuricemia model group, benzbromarone (3 mg/kg daily) intervention group and live Clostridium butyricum group (1.5×10(7) CFU/day)...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28460508/-effect-of-febuxostat-on-epithelial-to-mesenchymal-transition-of-kidney-tubules-serum-interleukin-6-and-transforming-growth-factor-%C3%AE-1-in-hyperuricemic-rats
#15
Z M Lin, R S Zhang, C X Fan, Y L Liang, L Li, L Zhao, J C Qu, X Xu, H Y Zhao, X N Liu, K S Zhu
Objective: To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF)β(1) in hyperuricemic rats. Methods: Forty male SD rats were divided into 4 groups: normal control group (NC group), oteracil potassium group (OP group), oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group). Each group had 10 rats and balanced in body weights. To induce hyperuricemia, rats were given oteracil potassium by gastric gavage once a day for eight weeks...
May 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28408375/uric-acid-is-associated-with-inflammatory-biomarkers-and-induces-inflammation-via-activating-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-hepg2-cells
#16
Rosangela Spiga, Maria Adelaide Marini, Elettra Mancuso, Concetta Di Fatta, Anastasia Fuoco, Francesco Perticone, Francesco Andreozzi, Gaia Chiara Mannino, Giorgio Sesti
OBJECTIVE: Serum uric acid (UA) has been associated with increased risk of cardiovascular and metabolic diseases. However, the causal mechanisms linking elevated UA levels to cardio-metabolic diseases are still unsettled. One potential explanation for how UA might contribute to cardio-metabolic disease might be its ability to induce systemic inflammation. APPROACH AND RESULTS: Herein, we report a positive relationship between serum UA and acute-phase reactants, such as high-sensitivity C-reactive protein, fibrinogen, ferritin, complement C3, and erythrocyte sedimentation rate, in a cohort of 2731 nondiabetic adults...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28386072/discovery-and-characterization-of-verinurad-a-potent-and-specific-inhibitor-of-urat1-for-the-treatment-of-hyperuricemia-and-gout
#17
Philip K Tan, Sha Liu, Esmir Gunic, Jeffrey N Miner
Gout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. Here, we characterize verinurad (RDEA3170), which is currently under evaluation for gout therapy. Verinurad specifically inhibits URAT1 with a potency of 25 nM. High affinity inhibition of uric acid transport requires URAT1 residues Cys-32, Ser-35, Phe-365 and Ile-481. Unlike other available uricosuric agents, the requirement for Cys-32 is unique to verinurad. Two of these residues, Ser-35 and Phe-365, are also important for urate transport kinetics...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28379501/cardiovascular-effects-of-urate-lowering-therapies-in-patients-with-chronic-gout-a-systematic-review-and-meta-analysis
#18
REVIEW
Tony Zhang, Janet E Pope
Objectives: To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes. Methods: Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors. Results: A total of 3084 citations were found, with 642 duplicates...
July 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/28365572/cost-effectiveness-analysis-for-genotyping-before-allopurinol-treatment-to-prevent-severe-cutaneous-adverse-drug-reactions
#19
Ching-Hua Ke, Wen-Hung Chung, Yen-Hsia Wen, Yaw-Bin Huang, Hung-Yi Chuang, You-Lin Tain, Yu-Ching Lily Wang, Cheng-Chih Wu, Chien-Ning Hsu
OBJECTIVE: Patients with an HLA-B*58:01 allele have an increased risk of developing severe cutaneous adverse drug reactions (SCAR) when treated with allopurinol. Although one-off pharmacogenetic testing may prevent life-threatening adverse drug reactions, testing prior to allopurinol initiation incurs additional costs. The study objective was to evaluate the cost-effectiveness of HLA-B*58:01 screening compared with using other available urate-lowering agents (ULA). METHODS: A decision-analytical model was used to compare direct medical costs and effectiveness [including lifetime saved, quality-adjusted life-yrs (QALY) gained] in treating new patients with the following options: (1) genetic screening followed by allopurinol prescribing for noncarriers of HLAB* 58:01, (2) prescribing benzbromarone without screening, (3) prescribing febuxostat without screening, and (4) prescribing allopurinol without screening...
April 1, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28357121/uricosuric-targets-of-tranilast
#20
Asim K Mandal, Adriana Mercado, Andria Foster, Kambiz Zandi-Nejad, David B Mount
Uric acid, generated from the metabolism of purines, has both proven and emerging roles in human disease. Serum uric acid in humans is determined by production and by the net balance of reabsorption and secretion in kidney and intestine. In the human kidney, epithelial reabsorption dominates over secretion, such that in normal subjects there is at least 90% net reabsorption of filtered urate resulting in a fractional excretion of <10%. Tranilast, an anti-inflammatory drug with pleiotropic effects, has a marked hypouricemic, uricosuric effect in humans...
April 2017: Pharmacology Research & Perspectives
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