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Benzbromarone

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https://www.readbyqxmd.com/read/29761242/safety-and-efficacy-of-benzbromarone-and-febuxostat-in-hyperuricemia-patients-with-chronic-kidney-disease-a-prospective-pilot-study
#1
Haibo Yu, Xinying Liu, Yaxiang Song, Jiafen Cheng, Hui Bao, Ling Qin, Xuan Zhou, Ling Wang, Ai Peng
BACKGROUND: To compare the safety and efficacy of benzbromarone and febuxostat in hyperuricemia patients with estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m2 . METHODS: This study was a single-centered, parallel-grouped, randomized clinical trial (RCT). We randomly assigned hyperuricemia participants with eGFR 20-60 mL/min/1.73 m2 into benzbromarone and febuxostat treatment group. Drugs were adjusted by titration from small doses. RESULTS: Seventy-three eligible participants enrolled, 66 subjects (33 in each group) were included finally for analysis...
May 14, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29721712/a-retrospective-analysis-of-medication-prescription-records-for-determining-the-levels-of-compliance-and-persistence-to-urate-lowering-therapy-for-the-treatment-of-gout-and-hyperuricemia-in-the-netherlands
#2
C A Janssen, M A H Oude Voshaar, H E Vonkeman, M Krol, M A F J van de Laar
Urate-lowering therapy (ULT) is a recommended life-long treatment for gout patients. However, despite these recommendations, recurrent gout attacks are commonly observed in clinical practice. The purpose of this study was to assess the levels of compliance and persistence to ULT in The Netherlands, in order to reflect on the current gout care delivered by health professionals. Anonymous prescription records were obtained from IQVIA's Dutch retrospective longitudinal prescription database, containing ULT dispensing data for allopurinol, febuxostat, and benzbromarone from November 2013 to July 2017...
May 2, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29719791/antihyperuricemic-effect-of-mangiferin-aglycon-derivative-j99745-by-inhibiting-xanthine-oxidase-activity-and-urate-transporter-1-expression-in-mice
#3
Zhizhen Qin, Shoubao Wang, Yihuang Lin, Ying Zhao, Shengqian Yang, Junke Song, Tao Xie, Jinlong Tian, Song Wu, Guanhua Du
A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days...
March 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29656005/the-uricosuric-effects-of-dihydropyridine-calcium-channel-blockers-in-vivo-using-urate-under-excretion-animal-models
#4
Takayuki Hori, Motoshi Ouchi, Naoyuki Otani, Masakatsu Nohara, Asuka Morita, Yusuke Otsuka, Promsuk Jutabha, Ikuko Shibasaki, Yasushi Matsushita, Tomoe Fujita, Hirotsugu Fukuda, Naohiko Anzai
The purpose of this study was to create novel urate under-excretion animal models using pyrazinamide and to evaluate whether dihydropyridine calcium channel blockers (CCBs) have uricosuric effects in vivo. Adult male ICR mice were treated with pyrazinamide, vehicle (dimethyl sulfoxide: DMSO), or tap water. Thirty minutes later, pyrazinamide-treated mice were given benzbromarone, losartan, nilvadipine, nitrendipine, nifedipine or azelnidipine. Six hours after the second administration, urine (by urinary bladder puncture) and plasma were collected to measure uric acid and creatinine levels, and fractional excretion of uric acid (FEUA) and creatinine clearance (Ccr) were calculated and evaluated...
March 8, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29566736/impact-of-diuretics-on-the-urate-lowering-therapy-in-patients-with-gout-analysis-of-an-inception-cohort
#5
Laura Ranieri, Carolina Contero, Maria-Luisa Peral, Irene Calabuig, Pedro Zapater, Mariano Andres
BACKGROUND: Diuretics have been associated with impaired response and refractoriness in gout, but whether this effect is still present with new urate-lowering drugs (ULD) and treat-to-target strategies is unknown. The aim of the present study was to assess the impact of the diuretics on the response to ULD in patients with gout.  METHODS: This was a retrospective analysis of an inception cohort. Participants were classified according to the type of ULD prescribed. We analysed the maximal dose of ULD (primary outcome variable), serum urate (SU) reduction, and the achievement of different SU targets (6 mg/dL, 5 mg/dL, and 4 mg/dL), according to the type of ULD prescribed and use of diuretics (loop and/or thiazide)...
March 22, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29526820/benzbromarone-aggravates-hepatic-steatosis-in-obese-individuals
#6
Peng Sun, Jing-Jie Zhu, Ting Wang, Qi Huang, Yu-Ren Zhou, Bang-Wei Yu, Hua-Liang Jiang, He-Yao Wang
As a widely used anti-gout drug, benzbromarone has been found to induce hepatic toxicity in patients during clinical treatment. Previous studies have reported that benzbromarone is metabolized via cytochrome P450, thus causing mitochondrial toxicity in hepatocytes. In this study, we found that benzbromarone significantly aggravated hepatic steatosis in both obese db/db mice and high fat diet (HFD)-induced obese (DIO) mouse models. However, benzbromarone had less effect on the liver of lean mice. It was found that the expression of mRNAs encoding lipid metabolism and some liver-specific genes were obviously disturbed in benzbromarone-treated DIO mice compared to the control group...
June 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29471754/anoctamin-channels-in-human-myometrium-a-novel-target-for-tocolysis
#7
Jennifer Danielsson, Joy Vink, Shunsuke Hyuga, Xiao Wen Fu, Hiromi Funayama, Ronald Wapner, Andrew M Blanks, George Gallos
BACKGROUND: Spontaneous preterm labor leading to preterm birth is a significant obstetric problem leading to neonatal morbidity and mortality. Current tocolytics are not completely effective and novel targets may afford a therapeutic benefit. OBJECTIVE: To determine whether the anoctamin (ANO) family, including the calcium-activated chloride channel ANO1, is present in pregnant human uterine smooth muscle (USM) and whether pharmacological and genetic modulation of ANO1 modulates USM contraction...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29382075/systematic-structure-activity-relationship-sar-exploration-of-diarylmethane-backbone-and-discovery-of-a-highly-potent-novel-uric-acid-transporter-1-urat1-inhibitor
#8
Wenqing Cai, Jingwei Wu, Wei Liu, Yafei Xie, Yuqiang Liu, Shuo Zhang, Weiren Xu, Lida Tang, Jianwu Wang, Guilong Zhao
In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds ( 1a - 1x and 1ha - 1hi ) were designed and synthesized, and their in vitro URAT1 inhibitory activities (IC50 ) were determined. The three-round systematic SAR exploration led to the discovery of a highly potent novel URAT1 inhibitor, 1h , which was 200- and 8-fold more potent than parent lesinurad and benzbromarone, respectively (IC50 = 0...
January 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29285235/eyes-absent-gene-eya1-is-a-pathogenic-driver-and-a-therapeutic-target-for-melanoma
#9
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
#10
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
#11
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...
March 2018: 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
#12
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
#13
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
#14
COMPARATIVE STUDY
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...
December 1, 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
October 2017: Journal of Biochemical and Molecular Toxicology
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