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Febuxostat

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https://www.readbyqxmd.com/read/29045766/population-pharmacodynamic-analysis-of-uric-acid-lowering-effects-of-febuxostat-based-on-electronic-medical-records-in-two-hospitals
#1
Shota Muraki, Kuniaki Moriki, Saki Shigematsu, Masato Fukae, Makoto Kakara, Daiki Yamashita, Takeshi Hirota, Hiroshi Takane, Miki Shimada, Masaaki Hirakawa, Ichiro Ieiri
The aim of this study was to develop a population pharmacodynamic (PPD) model to describe uric acid (UA)-lowering effects in patients treated with febuxostat based on electronic medical records in 2 independent hospitals (university and city hospitals). Interhospital differences in the PPD model were also evaluated. We conducted the following 2 approaches to build the PPD models. A PPD model was developed separately using individual hospital data, and structural models and covariates between the two hospitals were compared (approach A)...
October 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29028079/potency-on-lowering-serum-uric-acid-in-gout-patients-a-pooled-analysis-of-registrative-studies-comparing-febuxostat-vs-allopurinol
#2
M Cutolo, M A Cimmino, F Perez-Ruiz
OBJECTIVE: Hyperuricemia leading to urate crystal formation in tissues represents the pathophysiological mechanism of gout. Guidelines recommend a therapeutic target of serum urate concentration (sUA) <6 mg/dL, or even lower (≤5 mg/dL) in patients with large deposits. We conducted an analysis with the aim to achieve additional insights into the urate-lowering efficacy of two xanthine oxidase inhibitors, allopurinol and febuxostat. PATIENTS AND METHODS: This was a pooled analysis of phase III trials on allopurinol and febuxostat, including 4101 patients with gout and hyperuricemia...
September 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28982910/febuxostat-as-a-prophylaxis-for-tumor-lysis-syndrome-in-children-with-hematological-malignancies
#3
Kenji Kishimoto, Ryoji Kobayashi, Daiki Hori, Hirozumi Sano, Daisuke Suzuki, Kunihiko Kobayashi
AIM: The aim of the present study was to determine if febuxostat could prevent tumor lysis syndrome (TLS) in children who received induction chemotherapy for hematologic malignancies. PATIENTS AND METHODS: A retrospective analysis was performed in 45 pediatric patients with hematological malignancies who received febuxostat (10 mg daily, n=20) or allopurinol (300 mg/m(2) daily, n=25) as a prophylaxis for TLS. RESULTS: A significant decrease of serum uric acid (UA) level was observed in patients with febuxostat over the first 2 days (6...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28980503/lesinurad-a-selective-urat-1-inhibitor-with-a-novel-mechanism-in-combination-with-a-xanthine-oxidase-inhibitor-for-hyperuricemia-associated-with-gout
#4
Emily Huneycutt, Chase Board, Jennifer N Clements
OBJECTIVE: To review the pharmacokinetics, clinical efficacy, safety, and role of lesinurad for the management of hyperuricemia associated with gout. DATA SELECTION: A MEDLINE search (2000 to April 2017) was conducted using the terms hyperuricemia, gout, URAT-1, URAT-1 transporter, and lesinurad. Published articles and scientific posters relevant to the efficacy and safety of lesinurad were reviewed and summarized. DATA SYNTHESIS: Lesinurad was evaluated in 3 randomized, phase 3 clinical trials (CRYSTAL, CLEAR 1 and 2)...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28979780/lesinurad-what-the-nephrologist-should-know
#5
Maria Dolores Sanchez-Niño, Binbin Zheng-Lin, Lara Valiño-Rivas, Ana Belen Sanz, Adrian Mario Ramos, Jose Luño, Marian Goicoechea, Alberto Ortiz
Lesinurad is an oral inhibitor of the monocarboxylic/urate transporter URAT1 encoded by the SLC22A12 gene. Market authorization was granted in February 2016 in Europe and December 2015 in the USA. As a potentially nephrotoxic uricosuric drug acting on the kidney, nephrologists should become familiar with its indications and safety profile. The approved indication is treatment of gout in combination with a xanthine oxidase (XO) inhibitor in adult patients who have not achieved target serum uric acid levels with an XO inhibitor alone...
October 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28975718/effects-of-febuxostat-in-early-gout-a-randomized-double-blind-placebo-controlled-study
#6
Nicola Dalbeth, Kenneth G Saag, William E Palmer, Hyon K Choi, Barbara Hunt, Patricia A MacDonald, Ulrich Thienel, Lhanoo Gunawardhana
OBJECTIVES: To assess the effect of treatment with febuxostat vs placebo on joint damage in hyperuricemic subjects with early gout (experienced ≤2 gout flares). METHODS: In this double-blind, placebo-controlled study, subjects (n = 314) with hyperuricemia (serum uric acid [sUA] ≥7.0 mg/dL) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if sUA ≥6.0 mg/dL at day 14) or placebo. The primary efficacy endpoint was mean change from baseline (CFB) to month 24 in the modified Sharp-van der Heijde (mSvdH) erosion score from the single affected joint X-rays...
October 4, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28957559/cost-effectiveness-analysis-of-hla-b-58-01-genotyping-prior-to-initiation-of-allopurinol-for-gout
#7
REVIEW
Catrin O Plumpton, Ana Alfirevic, Munir Pirmohamed, Dyfrig A Hughes
Objective: To determine whether prospective testing for HLA-B*58:01, as a strategy to prevent serious adverse reactions to allopurinol in patients with gout, is cost-effective from the perspective of the National Health Service in the UK. Methods: A systematic review and meta-analysis for the association of HLA-B*58:01 with cutaneous and hypersensitivity adverse drug reactions informed a decision analytic and Markov model to estimate lifetime costs and outcomes associated with testing vs standard care (with febuxostat prescribed for patients who test positive)...
October 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/28933307/the-role-of-xanthine-oxidase-inhibitors-in-patients-with-history-of-stroke-a-systematic-review
#8
Sara R Britnell, Kelly A Chillari, Jamie N Brown
BACKGROUND: Xanthine oxidase inhibitors are commonly used to lower uric acid levels in patients with gout. Due to their effects on endothelial function, they have also been investigated for possible benefits for patients with cardiovascular disease. OBJECTIVE: To assess the efficacy and safety of xanthine oxidase inhibitors in the treatment of patients with history of stroke. METHODS: MEDLINE (1946-June 2017) and EMBASE (1947-June 2017) were queried using the search terms: "allopurinol" OR "febuxostat" OR "xanthine oxidase inhibitor" OR "xanthine oxidase/antagonists and inhibitors" AND "stroke" OR "cerebral infarction" OR "cerebrovascular accident"...
September 19, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28918097/synthesis-and-bioevaluation-of-1-phenyl-pyrazole-4-carboxylic-acid-derivatives-as-potent-xanthine-oxidoreductase-inhibitors
#9
Jing Li, Fangping Wu, Xingguo Liu, Yake Zou, Huixiong Chen, Zheng Li, Lei Zhang
A diverse library of 1-phenyl-pyrazole-4-carboxylic acid derivatives were synthesized and evaluated for their inhibitory potency against xanthine oxidoreductase (XOR) in vitro and vivo, and the structure-activity relationship (SAR) analyses were also presented. Approximately half of the target compounds exhibited the inhibitory potency for XOR at the nanomolar level. Compounds 16c, 16d, and 16f emerged as the most potent xanthine oxidoreductase inhibitors with IC50 values of 5.7, 5.7 and 4.2 nM, respectively, in comparison to febuxostat (IC50 of 5...
August 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28917757/innovative-thin-layer-chromatographic-method-combined-with-fluorescence-detection-for-specific-determination-of-febuxostat-application-in-biological-fluids
#10
Abdel-Maaboud I Mohamed, Mahmoud A Omar, Sayed M Derayea, Mohamed A Hammad, Abobakr A Mohamed
A newly developed thin-layer chromatographic (TLC) method coupled with fluorescence detection for specific determination of Febuxostat (FEB) was designed. The proposed method adopts exposure of FEB on a developed TLC plate to hydrochloric acid vapors, resulting in a large enhancement of its weak fluorescence, permitting its specific and sensitive determination in real human plasma and urine after excitation at 345nm on 60 F254 silica gel plates using toluene-ethyl acetate-methanol-glacial acetic acid; (30:10:5:0...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28904879/renoprotective-effects-of-febuxostat-compared-with-allopurinol-in-patients-with-hyperuricemia-a-systematic-review-and-meta-analysis
#11
Sollip Kim, Hyun-Jung Kim, Hyeong-Sik Ahn, Se Won Oh, Kum Hyun Han, Tae-Hyun Um, Chong-Rae Cho, Sang Youb Han
BACKGROUND: Hyperuricemia is reported to be related to rapid progression of renal function in patients with chronic kidney disease (CKD). Allopurinol, a uric acid lowering agent, protects renal progression. However, it is not widely used in patients with CKD because of its serious adverse event. Febuxostat can be alternatively used for patients who are intolerable to allopurinol. We aimed to determine renoprotective effect and urate-lowering effect between the two drugs. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials to assess the effects of febuxostat compared to allopurinol in patients with hyperuricemia...
September 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28904871/the-potential-renoprotection-of-xanthine-oxidase-inhibitors-febuxostat-versus-allopurinol
#12
EDITORIAL
Dong-Ryeol Ryu
No abstract text is available yet for this article.
September 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28888756/renoprotective-effect-of-the-xanthine-oxidoreductase-inhibitor-topiroxostat-under-decreased-angiotensin-ii-type-1a-receptor-expression
#13
Keiichi Ohata, Atsuko Kamijo-Ikemori, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Kimie Katayama, Junko Asano, Kenjiro Kimura, Yugo Shibagaki
The aim of this study was to confirm the renoprotective effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1a (AT1a) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1a expression, we used AT1a receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1a(+/-)L-FABP(+/-))...
September 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28888218/impact-of-non-adherence-on-the-safety-and-efficacy-of-uric-acid-lowering-therapies-in-the-treatment-of-gout
#14
Daniel Hill-McManus, Elena Soto, Scott Marshall, Steven Lane, Dyfrig Hughes
AIMS: Dual-urate lowering therapy (ULT) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout. Uricosurics can cause hyperuricosuria, a risk factor for nephrolithiasis and acute uric acid nephropathy. The aims of this study were to simulate the relation between suboptimal drug adherence and efficacy, and to quantify the risk of hyperuricosuria in gout patients receiving mono and dual-ULTs. METHODS: The impact of poor medication adherence was studied using 2-compartment PK models based on published evidence and a semi-mechanistic, 4-compartment pharmacodynamic (PD) model...
September 9, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28867729/comparison-of-clinical-advantage-between-topiroxostat-and-febuxostat-in-hemodialysis-patients
#15
Satoru Mitsuboshi, Hitoshi Yamada, Kazuhiko Nagai, Hideo Okajima
To determine the response of hemodialysis (HD) patients to topiroxostat after a switch from febuxostat, we evaluated the efficacy, tolerability, and serum concentration of topiroxostat in HD patients after the switch. In this 16-month prospective observational study, we assessed the serum uric acid (UA) levels, other laboratory data, and serum topiroxostat concentrations of 10 HD patients who had been receiving febuxostat at a dose of 10 mg/d for over 1 year. No statistical difference was observed between the tolerability index at baseline and 16 months after the switch to topiroxostat...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28801519/xor-inhibition-with-febuxostat-accelerates-pulmonary-endothelial-barrier-recovery-and-improves-survival-in-lipopolysaccharide-induced-murine-sepsis
#16
Mahendra Damarla, Laura F Johnston, Gigi Liu, Li Gao, Lan Wang, Lidenys Varela, Todd M Kolb, Bo S Kim, Rachel L Damico, Paul M Hassoun
Sepsis is a leading cause of death among patients in the intensive care unit, resulting from multi-organ failure. Activity of xanthine oxidoreductase (XOR), a reactive oxygen species (ROS) producing enzyme, is known to be elevated in nonsurvivors of sepsis compared to survivors. We have previously demonstrated that XOR is critical for ventilator-induced lung injury. Using febuxostat, a novel nonpurine inhibitor of XOR, we sought to determine the role of XOR inhibition in a murine model of sepsis-induced lung injury and mortality...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28693909/synthesis-and-evaluation-of-1-phenyl-1h-1-2-3-triazole-4-carboxylic-acid-derivatives-as-xanthine-oxidase-inhibitors
#17
Ting-Jian Zhang, Qing-Xia Wu, Song-Ye Li, Lin Wang, Qi Sun, Yi Zhang, Fan-Hao Meng, Hua Gao
This study mainly focused on the modification of the X(2) position in febuxostat analogs. A series of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives (1a-s) with an N atom occupying the X(2) position was designed and synthesized. Evaluation of their inhibitory potency in vitro on xanthine oxidase indicated that these compounds exhibited micromolar level potencies, with IC50 values ranging from 0.21µM to 26.13μM. Among them, compound 1s (IC50=0.21μM) showed the most promising inhibitory effects and was 36-fold more potent than allopurinol, but was still 13-fold less potent than the lead compound Y-700, which meant that a polar atom fused at the X(2) position could be unfavorable for potency...
August 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28689430/current-and-future-therapies-for-gout
#18
Tristan Pascart, Pascal Richette
Gout is a common disease responsible for recurrent flares triggered by the deposition of monosodium urate crystals secondary to longstanding hyperuricaemia. The management of gout implies both the treatment of flares and the treatment of hyperuricaemia itself. Recent improvement in the understanding of the disease led to the development of new drugs. Areas covered: This review covers data related to 'old' treatments of flares and hyperuricaemia, evidence on the recently approved drugs and emerging therapies in development...
July 28, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28682028/-the-uric-acid-cardio-nephropathy
#19
Francesca Viazzi, Barbara Bonino, Francesca Cappadona, Roberto Pontremoli
Uric acid is a product of purine catabolism formed by the activity of xanthine-oxidase and prevalently excreted by the kidney. In vivo, urate is known to have both an anti- or pro-oxidant role depending on several biological conditions. New evidence suggests that chronic hyperuricemia can contribute to hypertension development, kidney disease and cardiovascular risk. The pathophysiologic mechanisms are various, such as endothelial dysfunction and oxidative stress, vasoconstriction and stimulation of renin angiotensin system...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28679982/pseudomelanosis-duodeni-a-case-report
#20
Masaya Iwamuro, Shohei Oka, Hiromitsu Kanzaki, Takehiro Tanaka, Seiji Kawano, Yoshiro Kawahara, Hiroyuki Okada
An 83-year-old Japanese man underwent esophagogastroduodenoscopy for screening purposes. He had a medical history of hypertension, chronic kidney disease, chronic heart failure, and chronic myeloid leukemia, and he had been taking the following medications:ferrous citrate, furosemide, spironolactone, tolvaptan, bisoprolol, nicorandil, warfarin, nilotinib, febuxostat, esomeprazole, digestive enzyme complex, ambroxol, carbocysteine, and potassium L-aspartate. Esophagogastroduodenoscopy revealed a brownish speckled pigmentation in the duodenal bulb...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
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