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Febuxostat

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https://www.readbyqxmd.com/read/29660667/high-performance-thin-layer-chromatographic-methods-for-the-determination-of-febuxostat-and-febuxostat-diclofenac-combination-in-human-plasma
#1
Fawzi A El-Yazbi, Omayma A Amin, Eman I El-Kimary, Essam F Khamis, Sameh E Younis
Two simple, sensitive and specific high-performance thin-layer chromatographic (HPTLC) methods were developed for the determination of febuxostat (FEB) individually, and simultaneously with diclofenac (DIC) in human plasma. Method A presents the first HPTLC-ultraviolet attempt for FEB determination in human plasma. FEB was separated from endogenous plasma components (at hRF  = 70) with ethyl acetate-methanol-water (9:2:1, v/v) mixture as mobile phase and quantified by densitometry at its λmax (315 nm)...
April 10, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29657831/pharmacodynamic-and-pharmacokinetic-effects-and-safety-of-verinurad-in-combination-with-febuxostat-in-adults-with-gout-a-phase-iia-open-label-study
#2
Roy Fleischmann, Peter Winkle, Jesse Hall, Shakti Valdez, Sha Liu, Xiaohong Yan, Liz Hicks, Caroline Lee, Jeffrey N Miner, Michael Gillen, Martha Hernandez-Illas
Objective: Verinurad (RDEA3170) is a high-affinity, selective URAT1 inhibitor in development for treating gout and asymptomatic hyperuricaemia. This study evaluated the pharmacodynamics, pharmacokinetics and safety of verinurad in combination with febuxostat in adults with gout. Methods: The phase IIa, open-label, multicentre study randomised 64 subjects into one of five cohorts to receive febuxostat (40 or 80 mg) alone or in combination with verinurad 2.5-20 mg...
2018: RMD Open
https://www.readbyqxmd.com/read/29657221/unusual-cause-of-crystalline-nephropathy
#3
Natarajan Gopalakrishnan, Dhanasekaran Rajasekar, Jeyachandran Dhanapriya, Thanigachalam Dineshkumar, Ramanathan Sakthirajan, T Balasubramaniyan, V Murugesan
Adenine phosphoribosyltransferase deficiency is a rare, inherited autosomal recessive disease presenting with 2,8-dihydroxyadenine (DHA) urolithiasis, DHA nephropathy, and chronic kidney disease. The presence of DHA crystals in urine and renal biopsy is pathognomonic of the disease. We report a 23-year-old female with acute renal failure and nephrotic proteinuria. Urinalysis showed reddish brown, round crystals with dark outline, and central spicules consistent with 2,8-DHA crystals. Renal biopsy showed membranous nephropathy and 2,8-DHA nephropathy...
March 2018: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/29628139/drug-repurposing-in-kidney-disease
#4
REVIEW
Usha Panchapakesan, Carol Pollock
Drug repurposing, is the re-tasking of known medications for new clinical indications. Advantages, compared to de novo drug development, include reduced cost and time to market plus the added benefit of a known pharmacokinetic and safety profiles. Suitable drug candidates are identified through serendipitous observations, data mining, or increased understanding of disease mechanisms. This review highlights drugs suited for repurposing in kidney disease. The main cause of mortality in patients with chronic kidney disease is cardiovascular disease...
April 6, 2018: Kidney International
https://www.readbyqxmd.com/read/29622755/effects-of-pharmacological-reversal-of-hyperuricemia-on-features-of-the-metabolic-syndrome-in-patients-with-gouty-arthritis
#5
Mariana Marin, Naim M Maalouf
Hyperuricemia has been associated in epidemiological studies with the development of obesity, hypertension, insulin resistance and type 2 diabetes. Nevertheless, it remains unclear whether lowering of serum uric acid (UA) alters any of the features of the metabolic syndrome. In this prospective study (ClinicalTrials.gov identifier: NCT01654276), 24 patients with gouty arthritis and hyperuricemia were treated for 6 months with the xanthine oxidase inhibitor febuxostat to lower serum UA to <6 mg/dL. Measurements of 24 hours ambulatory blood pressure (ABP) and serum and urine markers of the metabolic syndrome were measured at baseline and at the end of 6 months of febuxostat...
April 4, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29597007/design-and-rationale-for-the-veterans-affairs-cooperative-study-program-594-comparative-effectiveness-in-gout-allopurinol-vs-febuxostat-trial
#6
S Timilsina, K Brittan, J R O'Dell, M Brophy, A Davis-Karim, A M Henrie, T Neogi, J Newcomb, P M Palevsky, M H Pillinger, D Pittman, T H Taylor, H Wu, T R Mikuls
BACKGROUND: Gout patients do not routinely achieve optimal outcomes related in part to suboptimal administration of urate lowering therapy (ULT) including first-line xanthine oxidase inhibitors allopurinol or febuxostat. Studies leading to the approval of febuxostat compared this agent to allopurinol in inappropriately low, fixed doses. We will compare allopurinol with febuxostat in gout using appropriately titrated doses of both agents and a "treat-to-target" strategy congruent with specialty guidelines...
March 26, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29595642/efficacy-of-febuxostat-in-hyperuricemic-patients-with-mild-to-moderate-chronic-kidney-disease-a-meta-analysis-of-randomized-clinical-trials-a-prisma-compliant-article
#7
Xiang Xia Zeng, Yunliang Tang, Kaixiang Hu, Xi Zhou, Jiao Wang, Lingyan Zhu, Jianying Liu, Jixiong Xu
BACKGROUND: To investigate the efficacy of febuxostat in hyperuricemic patients with chronic kidney disease (CKD), relevant randomized clinical trials (RCTs) were analyzed. METHODS: We used PubMed, Medline, ISI Web of Science, CBMdisc, and Cochrane Library databases to conduct a systematic literature research. A fixed-effects model was used to evaluate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). We conducted subgroup analysis, sensitivity analysis, and analyzed publication bias, to comprehensively estimate the renoprotective effects of febuxostat in hyperuricemic patients with CKD...
March 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29566736/impact-of-diuretics-on-the-urate-lowering-therapy-in-patients-with-gout-analysis-of-an-inception-cohort
#8
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/29557755/the-inhibitory-effect-of-some-drugs-on-candida-rugosa-lipase-and-pancreatic-human-lipase-in-vitro-and-in-silico-studies
#9
Talia Serseg, Khedidja Benarous
Side effects of some drugs may be useful in certain cases. In this work, we studied the inhibitory effects of some medications as: Folic Acid which is taken by pregnant women, Colchicine and Febuxostat which is used as treatment of gout disease. These cases are linked to obesity, where women (BMI ≥ 30) have twice higher odds of having an NTD-affected pregnancy than the normal weight women, and the Gout disease frequently occurs in combination of a Metabolic syndrome. The risk of gout increases with the increase of the mass index...
March 18, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29557073/cost-effectiveness-analysis-of-lesinurad-allopurinol-versus-febuxostat-for-the-management-of-gout-hyperuricemia-in-italy
#10
M Ruggeri, M Basile, C Drago, F R Rolli, A Cicchetti
BACKGROUND: Until very recently the only therapeutic alternative for the management of patients affected by gout/hyperuricemia that did not respond to a first-line treatment based on allopurinol alone or who cannot tolerate allopurinol was febuxostat, a xanthine oxidase non-purine-selective inhibitor. Lately, however, a new therapeutic alternative has become available for the management of this pathology: lesinurad, a urate transporter inhibitor. OBJECTIVE: To objective of this study was to evaluate the cost effectiveness of lesinurad/allopurinol in comparison with febuxostat as a second-line therapeutic strategy for the management of patients affected by gout and hyperuricemia that did not respond to a first-line therapy based on allopurinol alone...
March 19, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29547895/gout-state-of-the-art-after-a-decade-of-developments
#11
Tristan Pascart, Frédéric Lioté
This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management...
March 13, 2018: Rheumatology
https://www.readbyqxmd.com/read/29527974/cardiovascular-safety-of-febuxostat-or-allopurinol-in-patients-with-gout
#12
William B White, Kenneth G Saag, Michael A Becker, Jeffrey S Borer, Philip B Gorelick, Andrew Whelton, Barbara Hunt, Majin Castillo, Lhanoo Gunawardhana
Background Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease. Methods We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function...
March 12, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29497863/does-altered-uric-acid-metabolism-contribute-to-diabetic-kidney-disease-pathophysiology
#13
REVIEW
Ambreen Gul, Philip Zager
PURPOSE OF REVIEW: Multiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment. RECENT FINDINGS: In contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes...
March 1, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29497172/impaired-na-k-atpase-signaling-in-renal-proximal-tubule-contributes-to-hyperuricemia-induced-renal-tubular-injury
#14
Jing Xiao, Xiaoli Zhang, Chensheng Fu, Qingmei Yang, Ying Xie, Zhenxing Zhang, Zhibin Ye
Hyperuricemia contributes to renal inflammation. We aimed to investigate the role of Na+ -K+ -ATPase (NKA) in hyperuricemia-induced renal tubular injury. Human primary proximal tubular epithelial cells (PTECs) were incubated with uric acid (UA) at increasing doses or for increasing lengths of time. PTECs were then stimulated by pre-incubation with an NKA α1 expression vector or small interfering RNA before UA (100 μg ml-1 , 48 h) stimulation. Hyperuricemic rats were induced by gastric oxonic acid and treated with febuxostat (Feb)...
March 2, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29488355/individualized-treatment-strategies-for-hyperuricemia-informed-by-a-semi-mechanistic-exposure-response-model-of-uric-acid-dynamics
#15
Sergey Aksenov, Carl C Peck, Ulf G Eriksson, Donald R Stanski
To provide insight into pharmacological treatment of hyperuricemia we developed a semi-mechanistic, dynamical model of uric acid (UA) disposition in human. Our model represents the hyperuricemic state in terms of production of UA (rate, PUA), its renal filtration (glomerular filtration rate, GFR) and proximal tubular reabsorption (fractional excretion coefficient, FE). Model parameters were estimated using data from 9 Phase I studies of xanthine oxidase inhibitors (XOI) allopurinol and febuxostat and a novel uricosuric, the selective UA reabsorption inhibitor lesinurad, approved for use in combination with a XOI...
March 2018: Physiological Reports
https://www.readbyqxmd.com/read/29447788/the-influence-of-febuxostat-on-coronary-artery-endothelial-dysfunction-in-patients-with-coronary-artery-disease-a-phase-4-randomized-placebo-controlled-double-blind-crossover-trial
#16
Allison G Hays, Micaela Iantorno, Michael Schär, Shenghan Lai, Matthew Czarny, Elayne Breton, Robert N Palmer, Andrew Whelton, Robert G Weiss, Gary Gerstenblith
BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. METHODS: CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF...
March 2018: American Heart Journal
https://www.readbyqxmd.com/read/29447370/management-of-gout-by-uk-rheumatologists-a-british-society-for-rheumatology-national-audit
#17
Edward Roddy, Jon Packham, Karen Obrenovic, Ali Rivett, Joanna M Ledingham
Objectives: To assess the concordance of gout management by UK rheumatologists with evidence-based best-practice recommendations. Methods: Data were collected on patients newly referred to UK rheumatology out-patient departments over an 8-week period. Baseline data included demographics, method of diagnosis, clinical features, comorbidities, urate-lowering therapy (ULT), prophylaxis and blood tests. Twelve months later, the most recent serum uric acid level was collected...
February 13, 2018: Rheumatology
https://www.readbyqxmd.com/read/29415653/xanthine-oxidase-inhibitors-for-prevention-of-cardiovascular-events-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#18
Markus Bredemeier, Lediane Moreira Lopes, Matheus Augusto Eisenreich, Sheila Hickmann, Guilherme Kopik Bongiorno, Rui d'Avila, André Luis Bittencourt Morsch, Fernando da Silva Stein, Guilherme Gomes Dias Campos
BACKGROUND: Xanthine oxidase inhibitors (XOI), classified as purine-like (allopurinol and oxypurinol) and non-purine (febuxostat and topiroxostat) XOI, present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism. Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury, and may be implicated in the pathogenesis of heart failure, hypertension, and ischemic heart disease. However, there is contradictory evidence regarding the possible cardiovascular (CV) protective effect exerted by XOI...
February 7, 2018: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/29393124/treatment-of-hyperuricemia-in-chronic-kidney-disease
#19
Juan C Ramirez-Sandoval, Magdalena Madero
Hyperuricemia may be a major contributor to the development or progression of chronic kidney disease (CKD). Although there is no clear cutoff uric acid (UA) value associated to the risk for kidney damage, it appears to be an increased risk as UA rises. Lifestyle interventions such as exercise, weight reduction, low consumption of purine-rich meat, or avoiding high fructose intake are recommended for all hyperuricemic patients. Lowering urate drugs such as allopurinol or febuxostat may be an option as a renoprotective agent; yet, randomized clinical trials evaluating the safety and efficacy of these drugs are limited to a small number of single-center studies...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29390240/-hyperuricaemia-and-chronic-kidney-disease
#20
Carlo Garofalo, Toni De Stefano, Carlo Vita, Giorgia Vinci, Francesco Balia, Francesca Nettuno, Luisa Scarpati, Azzurra Sguazzo, Alessandra Sagliocchi, Mario Pacilio, Roberto Minutolo, Luca De Nicola, Silvio Borrelli
Hyperuricemia is defined as serum uric acid values greater than 6 mg/dl and could occur either due to hyperproduction or as a result of reduced renal excretion, which exceeds gut compensation. In Italy, prevalence is around 12% of the general population and increases in renal disease up to 60%. Recent experimental studies demonstrated a role of uric acid in the development of arterial hypertension and systemic arteriosclerosis, with an increase in cardiovascular risk. It also appears from observational studies that high uric acid is an independent risk factor associated with de novo onset of chronic kidney disease after adjustment of main confounding variables...
February 2018: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
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