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Febuxostat

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https://www.readbyqxmd.com/read/29906649/identification-of-new-drug-like-compounds-from-millets-as-xanthine-oxidoreductase-inhibitors-for-treatment-of-hyperuricemia-a-molecular-docking-and-simulation-study
#1
Rajesh Kumar Pathak, Ayushi Gupta, Rohit Shukla, Mamta Baunthiyal
Xanthine oxidoreductase plays an important role in formation of uric acid and its regulation during purine catabolism. Uncontrolled expression of this enzyme is responsible for overproduction and deposition of uric acid in blood that is potentially injurious because it can breakdown DNA and protein molecules, triggering many diseases. Human Xanthine oxidoreductase (HsXOR) is considered to be a pharmacological target for the treatment of hyperuricemia. Many of the HsXOR-inhibitor drugs such as Febuxostat and Allopurinol are known to have significant adverse effects...
May 28, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29899013/assessment-of-cardiovascular-risk-in-older-patients-with-gout-initiating-febuxostat-versus-allopurinol-a-population-based-cohort-study
#2
MaryAnn Zhang, Daniel H Solomon, Rishi J Desai, Eun Ha Kang, Jun Liu, Tuhina Neogi, Seoyoung C Kim
Background -Hyperuricemia and gout are associated with increased risk of cardiovascular disease (CVD). Xanthine oxidase inhibitors (XOI), allopurinol and febuxostat, are the mainstay of urate lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout. Methods -Using U.S. Medicare claims data (2008-2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among gout patients aged ≥65 years. The primary outcome was a composite endpoint of hospitalization for myocardial infarction (MI) or stroke...
June 13, 2018: Circulation
https://www.readbyqxmd.com/read/29885976/the-association-of-gout-with-incident-giant-cell-arteritis-in-older-adults
#3
Jasvinder A Singh, John D Cleveland
OBJECTIVES: To assess whether gout is associated with a higher or lower risk of a new diagnosis of giant cell arteritis (GCA) in older adults, adjusting for known risk factors of GCA. METHODS: We used the 5% Medicare claims to conduct a multivariable Cox regression analyses to assess the association of gout with incident GCA in adults 65 years or older adjusting for age, gender, race (known risk factors for GCA) and Charlson-Romano comorbidity score, the use of medications for cardiovascular diseases (statins, beta-blockers, diuretics, ACE-inhibitors) and gout (allopurinol, febuxostat)...
June 7, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29876951/evaluation-of-a-pharmacokinetic-pharmacodynamic-model-for-hypouricemic-effects-of-febuxostat-using-datasets-obtained-from-real-world-patients
#4
Toshinori Hirai, Toshimasa Itoh, Toshimi Kimura, Hirotoshi Echizen
AIM: Febuxostat is an active xanthine oxidase (XO) inhibitor that is widely used in the hyperuricemia treatment. We aimed to evaluate the predictive performance of a pharmacokinetic-pharmacodynamic (PK-PD) model for hypouricemic effects of febuxostat. METHODS: Previously, we have formulated a PK--PD model for predicting hypouricemic effects of febuxostat as a function of baseline serum urate levels, body weight, renal function, and drug dose using datasets reported in preapproval studies (Hirai T et al...
June 6, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29875169/cardiovascular-safety-of-febuxostat-and-allopurinol
#5
(no author information available yet)
No abstract text is available yet for this article.
June 6, 2018: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/29869840/implications-of-the-cardiovascular-safety-of-febuxostat-and-allopurinol-in-patients-with-gout-and-cardiovascular-morbidities-cares-trial-and-associated-fda-public-safety-alert
#6
REVIEW
Hyon Choi, Tuhina Neogi, Lisa Stamp, Nicola Dalbeth, Robert Terkeltaub
Recently, the FDA issued a public safety alert, responding to results of the now-published Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities (CARES) trial. CARES showed no significant difference between allopurinol and febuxostat in the primary composite endpoint of cardiovascular (CV) events in subjects with gout and established cardiovascular comorbidities at baseline. However, there was significantly increased risk of cardiac and all-cause mortality with febuxostat...
June 5, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29868853/verinurad-combined-with-febuxostat-in-japanese-adults-with-gout-or-asymptomatic-hyperuricaemia-a-phase-2a-open-label-study
#7
Masanari Shiramoto, Sha Liu, Zancong Shen, Xiaohong Yan, Amy Yamamoto, Michael Gillen, Yasushi Ito, Jesse Hall
Objectives: Verinurad (RDEA3170) is a high-affinity inhibitor of the URAT1 transporter in clinical development for treating gout and asymptomatic hyperuricaemia. The aim of this Phase 2a, randomized, open-label study was to investigate the multiple-dose pharmacodynamics, pharmacokinetics and safety of oral verinurad combined with febuxostat vs febuxostat alone and verinurad alone. Methods: Japanese male subjects aged 21-65 years with gout (n = 37) or asymptomatic hyperuricaemia (n = 35) and serum urate (sUA) ⩾8 mg/dl were randomized to febuxostat (10, 20, 40 mg) in combination with verinurad (2...
June 1, 2018: Rheumatology
https://www.readbyqxmd.com/read/29852375/spectroscopic-and-molecular-structure-monomeric-and-dimeric-model-investigation-of-febuxostat-a-combined-experimental-and-theoretical-study
#8
Jaya Pandey, Preeti Prajapati, Anubha Srivastava, Poonam Tandon, Kirti Sinha, Alejandro P Ayala, Arvind K Bansal
Febuxostat (FXT) is a urate-lowering drug and xanthine oxidase inhibitor which is used for the treatment of hyperuricemia and gout caused by increased levels of uric acid in the blood (hyperuricemia). The present study aims to provide deeper knowledge of the structural, vibrational spectroscopic and physiochemical properties of FXT based on monomeric and dimeric model with the aid of combination of experimental and computational methods. The conformational analysis of form Q has been done to predict the possible structure of unknown form A...
May 22, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29848361/efficacy-and-safety-of-febuxostat-extended-release-and-immediate-release-in-patients-with-gout-and-moderate-renal-impairment-phase-ii-placebo-controlled-study
#9
Lhanoo Gunawardhana, Michael A Becker, Andrew Whelton, Barbara Hunt, Majin Castillo, Kenneth Saag
BACKGROUND: Febuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended release (XR) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure. The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment (estimated glomerular filtrate rate ≥ 30 and < 60 ml/min)...
May 30, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29799494/side-effects-and-interactions-of-the-xanthine-oxidase-inhibitor-febuxostat
#10
REVIEW
Andreas Jordan, Ursula Gresser
The paper addresses the safety of febuxostat and summarizes reports on side effects and interactions of febuxostat published by the cut-off date (last day of literature search) of 20 March 2018. Publications on side effects and the interactions of febuxostat were considered. Information concerning the occurrence of side effects and interactions in association with the treatment with febuxostat was collected and summarized in the review. The incidence of severe side effects was much less frequent than mild side effects (1...
May 25, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29797773/baseline-characteristics-of-the-autosomal-dominant-polycystic-kidney-disease-subcohort-of-the-korean-cohort-study-for-outcomes-in-patients-with-chronic-kidney-disease-know-ckd
#11
Hyunsuk Kim, Junga Koh, Sue K Park, Kook Hwan Oh, Yeong Hoon Kim, Yaeni Kim, Curie Ahn, Yun Kyu Oh
AIM: The aim of this study was to describe the baseline characteristics of autosomal dominant polycystic kidney disease (ADPKD) in a cohort of Korean patients with chronic kidney disease (CKD). METHODS: From April 2011 to February 2016, patients with CKD stage 1 to 5 (pre-dialysis) were enrolled as an ADPKD subcohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease. Baseline characteristics, the correlation of kidney and liver volume and kidney function, and the factors associated with kidney function were analyzed...
May 24, 2018: Nephrology
https://www.readbyqxmd.com/read/29786457/xanthine-oxidase-inhibitors-and-sepsis
#12
Maria Fátima de Paula Ramos, Alceni do Carmo Morais Monteiro de Barros, Clara Versolato Razvickas, Fernanda T Borges, Nestor Schor
Xanthine oxidase activation occurs in sepsis and results in the generation of uric acid (UrAc) and reactive oxygen species (ROS). We aimed to evaluate the effect of xanthine oxidase inhibitors (XOis) in rats stimulated with lipopolysaccharide (LPS). LPS (10 mg/kg) was administered intraperitoneally (i.p.) immediately after allopurinol (Alo, 2 mg/kg) or febuxostat (Feb, 1 mg/kg) every 24 h for 3 days. To increase UrAc levels, oxonic acid (Oxo) was administered by gavage (750 mg/kg per day) for 5 days...
January 2018: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/29772470/synthesis-molecular-docking-and-xanthine-oxidase-inhibitory-activity-of-5-aryl-1h-tetrazoles
#13
Itrat Fatima, Humaira Zafar, Khalid Mohammed Khan, Syed Muhammad Saad, Sumaira Javaid, Shahnaz Perveen, M Iqbal Choudhary
5-Aryl-1H-tetrazoles (1-24) were synthesized and screened for their xanthine oxidase (XO) inhibitory activity using allopurinol as standard inhibitor (IC50  = 2.0 ± 0.01 µM). Six compounds 3, 4, 5, 9, 21, and 24 exhibited significant to weak activities with IC50 values in the range of 7.4-174.2 µM. Active compounds were further subjected to kinetic and molecular docking studies to deduce their modes of inhibition, and to study their interactions with the protein (XO) at atomic level, respectively...
May 1, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29761242/safety-and-efficacy-of-benzbromarone-and-febuxostat-in-hyperuricemia-patients-with-chronic-kidney-disease-a-prospective-pilot-study
#14
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/29750634/effectiveness-of-febuxostat-in-patients-with-allopurinol-refractory-hyperuricemic-chronic-kidney-disease
#15
Chae Hee Kwak, Minji Sohn, Nayoung Han, Yoon-Sook Cho, Yon Su Kim, Jung Mi Oh
OBJECTIVE: As uncontrolled hyperuricemia has been associated with an increased risk of cardiovascular disease and the progression of chronic kidney disease (CKD), management of serum uric acid levels is important. The aim of this study was to evaluate the effectiveness of febuxostat in regulating uncontrolled hyperuricemia in patients with renal dysfunction. MATERIALS AND METHODS: We included patients with CKD and persistent uncontrolled hyperuricemia despite treatment with allopurinol...
May 11, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29725991/retreatment-with-pegloticase-after-a-gap-in-therapy-in-patients-with-gout-a-report-of-four-cases
#16
Allan H Morton, Tony Hosey, Brian LaMoreaux
INTRODUCTION: Pegloticase, a potent uricolytic biologic enzyme, has been shown to be an effective therapeutic option in patients with uncontrolled gout. However, there are limited data on clinical response after a gap in therapy and retreatment with pegloticase. CASE SERIES: This report describes four patients with chronic gout who were successfully managed with pegloticase and were retreated following a gap in therapy. Patient charts from a practice-based rheumatology clinic were retrospectively analyzed; four male patients, aged 70-75 years, with chronic gout and a more than 4-week gap in pegloticase therapy were reviewed...
May 3, 2018: Rheumatology and Therapy
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
#17
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/29700702/the-impact-of-serum-uric-acid-reduction-on-renal-function-and-blood-pressure-in-chronic-kidney-disease-patients-with-hyperuricemia
#18
Takayuki Tsuji, Kazuhisa Ohishi, Asumi Takeda, Daiki Goto, Taichi Sato, Naro Ohashi, Yoshihide Fujigaki, Akihiko Kato, Hideo Yasuda
BACKGROUND: Febuxostat is tolerable in chronic kidney disease (CKD) patients with hyperuricemia. However, the long-term effect of lowering uric acid with febuxostat on renal function and blood pressure has not been elucidated. METHODS: This was a 2 years retrospective observational study. 86 CKD patients with hyperuricemia who continued with allopurinol (allopurinol group, n = 30), switched from allopurinol to febuxostat (switched group, n = 25), or were newly prescribed febuxostat (febuxostat group, n = 31) were included in this study...
April 26, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29689561/urate-lowering-agents-in-asymptomatic-hyperuricemia-role-of-urine-sediment-analysis-and-musculoskeletal-ultrasound
#19
Davide Viggiano, Giuseppe Gigliotti, Gianfranco Vallone, Anna Giammarino, Michelangelo Nigro, Giovambattista Capasso
Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four 'indirect' drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum...
2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29688628/pharmacokinetics-pharmacodynamics-and-tolerability-of-concomitant-administration-of-verinurad-and-febuxostat-in-healthy-male-volunteers
#20
Jesse Hall, Michael Gillen, Xiaojuan Yang, Zancong Shen
Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in development for treatment of gout and asymptomatic hyperuricemia. This phase 1, single-blind, multiple-dose, drug-drug interaction study evaluated the pharmacokinetics (PK), pharmacodynamics, and safety/tolerability of verinurad in combination with febuxostat in healthy male volunteers. Twenty-three subjects were randomized and received once-daily doses of verinurad (or placebo) or febuxostat alone (days 1-7 and days 15-21), or verinurad + febuxostat on days 8-14...
April 24, 2018: Clinical Pharmacology in Drug Development
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