scholarly journals Xanthine oxidase inhibitors are associated with reduced risk of cardiovascular disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirotaka Saito ◽  
Kenichi Tanaka ◽  
Tsuyoshi Iwasaki ◽  
Akira Oda ◽  
Shuhei Watanabe ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Xanthine Oxidase ◽  
Cardiovascular Events ◽  
Oxidase Inhibitor ◽  
Cardiovascular Risks ◽  
Diabetic Mellitus ◽  
Xanthine Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitors ◽  
Reduced Risk

AbstractAs previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19–2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26–0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.

Abstract 12506: Therapeutic Strategy for Efficient Reduction of Serum Uric Acid With Allopurinol versus Benzbromarone in Hyperuricemic Patients With Cardiovascular Disease ~ A Randomized Crossover Study (TERAO study) ~

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sunao Kojima ◽  
Shinobu Kojima ◽  
Hirofumi Soejima ◽  
Hisao Ogawa
Keyword(s):  
Cardiovascular Disease ◽  
Uric Acid ◽  
Crossover Study ◽  
Xanthine Oxidase ◽  
Serum Uric Acid ◽  
Cardiovascular Events ◽  
Oxidase Inhibitor ◽  
Creatinine Ratio ◽  
Cardiovascular Risks ◽  
Xanthine Oxidase Inhibitor

Introduction: Hyperuricemia is considered to be a marker of future cardiovascular events. Uricosuric agents and urate synthesis inhibitors has been widely used in hyperuricemic patients. Hypothesis: We assessed the hypothesis that the different mechanism of these drugs has an impact on urine albumin-creatinine ratio (ACR) associated with cardiovascular risks. Methods: A total of 14 hyperuricemic patients (serum uric acid levels >7 mg/dL) with cardiovascular disease were randomly assigned and treated with either benzbromarone, 25mg once daily, or allopurinol, 200 mg twice daily for 2 weeks, followed by a 2-week washout period, then a 2-week crossover phase. Results: Serum uric acid levels were comparable and similarly reduced with benzbromarone (8.4±1.1→4.8±1.3 mg/dL, P<0.0001) and allopurinol (8.4±1.0→5.1±0.9 mg/dL, P<0.0001). However, allopurinol significantly reduced urine ACR compared with benzbromarone (Figure 1). A logistic regression analysis revealed that influential clinical factors on reduced urine ACR were not observed except for allopurinol administration. The change of urine ACR was positively correlated with the change of urinary urate-creatinine ratio (UCR), indicating a substitution for xanthine oxidase activity (Figure 2). Conclusions: In this short-term, crossover study in hyperuricemic patients with cardiovascular disease, a treatment with xanthine oxidase inhibitor resulted in a reduction of urine ACR. These results represent a novel potential therapeutic approach with antioxidant strategy, which may lead to a reduction of future cardiovascular events. These preliminary findings require confirmation in larger clinical trials.

Hyperuricemia Resistant to a Xanthine Oxidase Inhibitor, Topiroxostat: a Case Report

2021 ◽  
Author(s):  
Takahide Kimura ◽  
Seiki Yamada ◽  
Masayuki Tanemoto
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Oxidase Inhibitor ◽  
Uric Acid Concentration ◽  
Common Complication ◽  
Xanthine Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitors ◽  
Serum Uric Acid Concentration ◽  
Rate Limiting

Abstract Hyperuricemia is a common complication of chronic kidney disease. Gout is a clinical symptom of hyperuricemia, and lowering serum uric acid concentration has been recommended to prevent its recurrence. We present a case whose hyperuricemia was resistant to a xanthine oxidase inhibitor, febuxostat, but not another inhibitor, topiroxostat, while both are presumed to inhibit the same enzymatic center of this rate-limiting enzyme for uric acid production. The different efficacy indicates that xanthine oxidase inhibitors are not interchangeable even among those acting on the same site of the enzyme.

Efficacy of xanthine oxidase inhibitor for chronic kidney disease patients with hyperuricemia

2019 ◽  
Vol 24 (4) ◽  
pp. 307-313
Author(s):  
Hiroshi Matsuo ◽  
Eiji Ishikawa ◽  
Hirofumi Machida ◽  
Yasuhide Mizutani ◽  
Akiko Tanoue ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Xanthine Oxidase ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor

Principles of gout management

2016 ◽  
Author(s):  
Pascal Richette
Keyword(s):  
Xanthine Oxidase ◽  
Interleukin 1 ◽  
Serum Urate ◽  
Oxidase Inhibitor ◽  
Tophaceous Gout ◽  
Xanthine Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitors ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
General Goals

The general goals of gout therapy are to manage acute flares and to prevent recurrences and prevent or reverse the complications of urate deposition by lowering urate levels. The choice of drug should be made on the basis of the patient’s co-morbidities, other medications, and side effect profile. Treatment of flares can be achieved with non-steroidal anti-inflammatory drugs, colchicine, or corticosteroids (systemic or intra-articular). Interleukin-1 blockers could become an alternative in patients contraindicated for traditional anti-inflammatory agents. Lowering of urate levels below monosodium urate (MSU) saturation point with both a non-pharmacological and pharmacological approach allows to dissolve MSU crystals and to cure gout. Serum urate (SUA) levels should be maintained below 6 mg/dL (360 μ‎mol/L) or below 5 mg/dL (300 μ‎mol/L) in patients with severe gout to facilitate faster dissolution of crystals. Urate-lowering therapy (ULT) should be initiated close to the first diagnosis of gout. Allopurinol and febuxostat are the most widely used xanthine oxidase inhibitors to lower SUA levels. If the SUA target cannot be reached by these agents, uricosurics are indicated, either alone or in combination with a xanthine oxidase inhibitor. In patients with severe tophaceous gout in whom the SUA target cannot be reached with any other available drug, pegloticase is indicated. Since ULT initiation may trigger acute attacks of gout, prophylaxis with an anti-inflammatory agent is recommended, mostly with low-dose colchicine. Of note, patient education, appropriate lifestyle advice, and treatment of comorbidities are also important parts of the management of patients with gout.

Transport and metabolism of 6-thioguanine and 6-mercaptopurine in mouse small intestine

1988 ◽  
Vol 74 (6) ◽  
pp. 629-638 ◽  
Author(s):  
J. R. Bronk ◽  
Norma Lister ◽  
M. I. Shaw
Keyword(s):  
Small Intestine ◽  
Xanthine Oxidase ◽  
Drug Concentration ◽  
Time Course ◽  
Oxidase Inhibitor ◽  
Unknown Compound ◽  
Xanthine Oxidase Inhibitor ◽  
Drug Concentrations ◽  
Xanthine Oxidase Inhibitors ◽  
Mouse Small Intestine

1. The transport of 6-thioguanine and 6-mercaptopurine has been studied with isolated jejunal loops of mouse small intestine. H.p.l.c. was used to identify and quantify the thiopurines and their metabolites in the serosal secretions. 2. When the lumen of the intestinal loops contained either 6-thioguanine or 6-mercaptopurine at a concentration of 1 mmol/l, the concentration of unmetabolized drug in the serosal secretions reached a maximum of 0.13 ± 0.02 mmol/l (mean ± sem). 3. Analysis of the serosal secretions from the perfusions with either of the drugs revealed the appearance of an unknown compound which had the characteristics of a thiopurine and the same time course of appearance as the unmetabolized drug. Thus 6-thioguanine and 6-mercaptopurine are significantly metabolized during absorption in mouse intestine. 4. The unknown compound was identified as 6-thiouric acid, and with 1 mmol/l 6-thioguanine or 6-mercaptopurine in the lumen the concentration of this metabolite in the serosal secretions rose to a maximum of 0.13 ± 0.01 and 0.18 ± 0.03 mmol/l, respectively. At luminal drug concentrations of 0.1 mmol/l, the metabolite accounted for approximately 90% of the serosal thiopurine. 5. After an initial lag period of 20 min, linear rates of appearance in the serosal secretions were obtained for both the unmetabolized drugs and 6-thiouric acid. 6. Addition of the xanthine oxidase inhibitor oxypurinol at a luminal concentration of 0.3 mmol/l prevented the formation of 6-thiouric acid from 6-thioguanine. However, the inhibitor reduced the rate of 6-thioguanine appearance in the serosal secretions by 50%. 7. The conversion of 6-mercaptopurine to 6-thiouric acid was prevented when allopurinol or oxypurinol were added to the lumen. At a luminal drug concentration of 1 mmol/l, allopurinol increased the rate at which 6-mercaptopurine appeared in the serosal secretions by 90% compared with an increase of only 50% with oxypurinol. 8. The transport of water and glucose by the mouse intestinal loops was unaffected by 6-thioguanine or the xanthine oxidase inhibitors. However, 6-mercaptopurine caused significant reductions in the rate of water transport (30%) and glucose transport (39%). These effects were observed at a luminal drug concentration of 0.1 mmol/l and there was no further increase at a drug concentration of 1 mmol/l.

FUNGAL ENDOPHYTES AS REPOSITORY OF XANTHINE OXIDASE INHIBITOR

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (03) ◽  
pp. 7-11
Author(s):  
N. Kapoor ◽  
S. Saxena ◽  
L. Gambhir ◽  
Keyword(s):  
Xanthine Oxidase ◽  
Endophytic Fungi ◽  
Fungal Endophytes ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
Therapy Regimen ◽  
Xanthine Oxidase Inhibitors ◽  
Key Enzyme ◽  
Anti Oxidant ◽  
And Oxidative Stress

Xanthine oxidase, a key enzyme of purine metabolism, is considered to be a prime target for the treatment of hyperuricemia and oxidative stress related disorders. Allopurinol and febuxostat are two FDA approved xanthine oxidase inhibitors currently being used for management of chronic hyperuricemia. Plethora of natural sources has been explored in search of novel chemical templates for the development of antihyperuricemic drugs. Studies in past decade have shown the potential of endophytic fungi, which colonize the internal tissues of plants without any evident sign of their ubiquitous existence, as repository of novel chemical entities exhibiting antimicrobial, anti-oxidant, anti-inflammatory and anticancer potential. However, very scanty preliminary data is available of exploration of xanthine oxidase inhibitors from fungal endophytes. The present review summarizes the efficacy of xanthine oxidase as target for developing ant-gout agents and highlights the prospective of endophytic fungi as producers of xanthine oxidase inhibitors for the anti-hyperuricemic therapy regimen.

scholarly journals Clinical Effects of Xanthine Oxidase Inhibitors in Hyperuricemic Patients

2020 ◽  
Author(s):  
Arrigo F.G. Cicero ◽  
Federica Fogacci ◽  
Raffaele Ivan Cincione ◽  
Giuliano Tocci ◽  
Claudio Borghi
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
English Language ◽  
Clinical Evidence ◽  
Oxidase Inhibitor ◽  
Clinical Effects ◽  
Xanthine Oxidase Inhibitor ◽  
Positive Effects ◽  
Xanthine Oxidase Inhibitors ◽  
First Choice

This review aim is to critically resume the available clinical evidence supporting the treatment of chronic hyperuricemia with xanthine-oxidase inhibitor activity. For this reason, all of the studies published in English language from 2000 to August 2019 on uric acid-lowering drugs have been carefully reviewed. The terms “serum uric acid”, “xanthine oxidase”, “allopurinol”, “febuxostat”, and “topiroxostat” have been incorporated into an electronic search strategy, alone and in combinations, in both MEDLINE (National Library of Medicine, Bethesda, MD) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). Even if new urate lowering drugs seem of particular efficacy for acute treatment of refractory hyperuricemia, their use is supported by relatively small clinical evidence: On the contrary, large long-term clinical trials have clearly demonstrated that xanthine oxidase inhibitors (namely, allopurinol and febuxostat) are effective, safe and relatively well-tolerated in the most part of patients. They have been largely tested in elderly, in patients affected by crhonic diseases such as heart failure and cancer, and in patients taking a large number of drugs, confirming their safety profile. Recent data also show that they could exert some positive effects on vascular health, renal function and glucose metabolism. Their cost is also low. In conclusion, xanthine oxidase inhibitors remain the first choice uric acid lowering drug for chronic treatment.

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