scholarly journals Dapagliflozin Added to Verinurad Plus Febuxostat Further Reduces Serum Uric Acid in Hyperuricemia: The QUARTZ Study

2020 ◽  
Author(s):  
Austin G Stack ◽  
David Han ◽  
Ronald Goldwater ◽  
Susanne Johansson ◽  
Nalina Dronamraju ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Oxidase Inhibitor ◽  
Renal Tubules ◽  
Clinical Trial Registration ◽  
Xanthine Oxidase Inhibitor ◽  
Once Daily ◽  
Glucose Levels ◽  
Safety Parameters ◽  
Excretion Rates

Abstract Context Combining a sodium-glucose cotransporter 2 inhibitor with a xanthine oxidase inhibitor (XOI) and a urate transporter 1 (URAT1) inhibitor may enhance serum uric acid (sUA) lowering. However, concerns exist regarding high urinary UA (uUA) excretion rates and subsequent crystallization in renal tubules. Objective To assess whether dapagliflozin added to verinurad, a selective URAT1 inhibitor, and febuxostat, an XOI, increases uUA excretion. Design Randomized, placebo-controlled, 2-way crossover study (NCT03316131). Patients Adults with asymptomatic hyperuricemia. Interventions Subjects (N = 36) were randomized to oral once-daily 9 mg verinurad plus 80 mg febuxostat plus 10 mg dapagliflozin for 7 days and 7 days of oral once-daily 9 mg verinurad plus 80 mg febuxostat plus placebo with an intervening 7- to 21-day washout period. Main Outcome Measure Difference in peak uUA excretion between groups from baseline to day 7. Secondary outcomes included changes in sUA levels and 24-h uUA excretion. Results Both regimens lowered mean peak uUA excretion (least squares mean changes from baseline: −12.9 mg/h [95% confidence interval (CI): −21.0 to −4.7], dapagliflozin; −13.2 mg/h [95% CI −21.3 to –5.0], placebo). sUA concentrations were lower with dapagliflozin (mean treatment difference –62.3 µmol/L [95% CI −82.8 to −41.8]). Dapagliflozin did not impact verinurad pharmacokinetics, its main metabolites, or febuxostat or fasting plasma glucose levels vs verinurad plus febuxostat. There were no clinically relevant changes in safety parameters. Conclusions Dapagliflozin further reduced sUA without influencing uUA excretion, suggesting that its combination with verinurad and febuxostat at the doses tested does not adversely affect kidney function. Clinical trial registration number NCT03316131.

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.

scholarly journals Urate Lowering Therapy with Febuxostat in Daily Practice—A Multicentre, Open-Label, Prospective Observational Study

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Anne-Kathrin Tausche ◽  
Monika Reuss-Borst ◽  
Ute Koch
Keyword(s):  
Uric Acid ◽  
Observational Study ◽  
Serum Uric Acid ◽  
Prospective Observational Study ◽  
Treatment Effectiveness ◽  
Daily Practice ◽  
Oxidase Inhibitor ◽  
Open Label ◽  
Xanthine Oxidase Inhibitor ◽  
Urate Lowering Treatment

Introduction.Febuxostat, a novel xanthine oxidase inhibitor for the treatment of symptomatic hyperuricemia, showed superiority over allopurinol in the reduction of serum uric acid levels in pivotal studies. Whether this holds true the FORTE (febuxostat in the oral urate lowering treatment: effectiveness and safety) study was conducted to evaluate treatment with febuxostat under daily practice conditions.Materials/Methods.The multicentre, open-label, and prospective observational study was conducted in 1,690 German medical practices from 9/2010 to 5/2011. Safety and efficacy data were assessed at baseline and week 4.Results.Data from 5,592 gout patients (72.6% male, mean age 63.7 years) were collected. Under urate lowering treatment with febuxostat mean serum uric acid levels decreased significantly from8.9±1.9 mg/dL (534.0±114.6 μmol/L) at baseline to6.2±2.5 mg/dL (372.0±150.0 μmol/L) at week 4. 67% which reached the mean uric acid target (6.1±1.0 mg/dL [366.0±59.4 μmol/L]). Only 43.1% of patients received concomitant flare prophylaxis. A total of 178 adverse events (mostly gout flares) were reported in 152 patients (2.6%).Conclusion.Febuxostat lowers serum uric acid levels effectively in routine clinical practice. Overall, treatment with febuxostat in both available dosages (80 mg/120 mg) was safe and well tolerated.

scholarly journals Metabolic and cardiovascular effects of chronic mild hyperuricemia in rodents

2018 ◽  
Vol 66 (7) ◽  
pp. 1037-1044
Author(s):  
Sun K Park ◽  
Tara R Rosenthal ◽  
Jessica S Williams ◽  
John M Shelton ◽  
Masaya Takahashi ◽  
...  
Keyword(s):  
Uric Acid ◽  
Glucose Tolerance ◽  
Serum Uric Acid ◽  
Glucose Intolerance ◽  
Fasting Glucose ◽  
Elevated Serum ◽  
Cardiovascular Effects ◽  
Oxidase Inhibitor ◽  
Sprague Dawley ◽  
Xanthine Oxidase Inhibitor

Mildly elevated serum uric acid levels are common in people with metabolic syndrome and type 2 diabetes mellitus (T2DM), but whether elevated uric acid has a causal role in the pathogenesis of diabetes remains uncertain. We tested whether chronic mild hyperuricemia in rodents under controlled laboratory conditions can cause glucose intolerance in otherwise healthy animals, or whether it can worsen glucometabolic control in animals that are genetically predisposed to T2DM. We used an established model of experimental hyperuricemia in rodents with potassium oxonate dietary supplementation, which led to sustained, approximately two-fold elevation of uric acid compared with control animals. We also reversed the hyperuricemic effect of oxonate in some animals by treatment with a xanthine oxidase inhibitor. Manipulation of serum uric acid levels in Sprague-Dawley rats for up to 18 weeks did not affect fasting glucose and glucose tolerance. Blood pressure was also not affected by hyperuricemia in rats fed a Western-type diet. We next sought to determine whether uric acid may aggravate or accelerate the onset of glucometabolic abnormalities in rats already predisposed to T2DM. Chronic oxonate treatment in Zucker diabetic fatty (ZDF) and lean control rats for up to 6 weeks did not affect fasting glucose, insulin, and glucose tolerance in ZDF rats. Taken together, these findings indicate that elevated uric acid does not directly contribute to the pathogenesis of glucose intolerance and T2DM in rodents.

Simultaneous Monitoring of Febuxostat and Uric Acid in Human Serum Samples Using the Direct Square-Wave Voltammetric Method

2019 ◽  
Vol 15 (6) ◽  
pp. 678-684
Author(s):  
Biljana Nigović ◽  
Jakov Vlak
Keyword(s):  
Uric Acid ◽  
Human Serum ◽  
Oxidase Inhibitor ◽  
Serum Samples ◽  
Boron Doped Diamond ◽  
Fast Analysis ◽  
Xanthine Oxidase Inhibitor ◽  
Voltammetric Method ◽  
Square Wave ◽  
Human Serum Samples

Background: High uric acid serum level, hyperuricemia, is now associated with many diseases such as gout, chronic kidney disease, hypertension, coronary artery disease and diabetes. Febuxostat is a novel selective xanthine oxidase inhibitor approved for the treatment of hyperuricemia. Objective: The aim of this study was to develop a first analytical method for the simultaneous determination of febuxostat and uric acid. Methods: An unmodified boron-doped diamond electrode provided concurrent quantitation of drug at low levels and uric acid, which has clinical significance in the diagnosis and therapy of hyperuricemia, at relatively high concentrations. The direct square-wave voltammetric method was applied to the analysis of both analytes in human serum samples. Results: Under the optimized conditions, the linear response of peak current on febuxostat concentration was achieved in the range from 7.5 × 10-7 to 3 × 10-5 M, while uric acid showed two linear ranges of 5 × 10-6 - 5 × 10-5 M and 5 × 10-5 - 2 × 10-4 M. The method was successfully utilised for quantification of both analytes in human serum samples. Good recoveries were obtained without interference from common inorganic cations and anions as well as glucose, dopamine, ascorbic and folic acids at concentrations expected in physiological conditions. Conclusion: The great benefits of developed method are fast analysis (only 7.5 s for run), low cost and simplicity of performance.

Allopurinol and Loss of Consciousness in a 78-old Year Man Suffering from Gout

2020 ◽  
Vol 20 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Mahnaz Arian ◽  
Mina AkbariRad ◽  
Ahmad Bagheri Moghaddam ◽  
Abdollah Firoozi ◽  
Mohammad Jami
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Kidney Stones ◽  
Oxidase Inhibitor ◽  
Loss Of Consciousness ◽  
Drug Induced ◽  
Xanthine Oxidase Inhibitor ◽  
Case Presentation ◽  
Maculopapular Rashes ◽  
Reduced State

: Allopurinol is an FDA -Approved xanthine oxidase inhibitor, which is effective in the treatment of gout, hyperuricemia and uremic kidney stones in patients with an increased level of uric acid excretion. Xanthine oxidase acts by converting hypoxanthine and xanthine into uric acid, and therefore its inhibition results in decreased production of uric acid. The most common side effects of this medication are as follows: maculopapular rashes, hives, itching, headache, dizziness, abnormal hair loss, fever and hypersensitivity reaction. Case Presentation: This report represents a case of drug-induced meningitis of a senile man who ended up in the ICU due to the remarkably reduced state of consciousness.

Fluorometric determination of uric acid in bovine milk

2010 ◽  
Vol 77 (4) ◽  
pp. 438-444 ◽  
Author(s):  
Torben Larsen ◽  
Kasey M Moyes
Keyword(s):  
Heat Treatment ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Bovine Milk ◽  
Oxidase Inhibitor ◽  
Enzymatic Oxidation ◽  
Fast Method ◽  
Xanthine Oxidase Inhibitor ◽  
Milk Samples

The primary objective of this study is to validate a new fast method for determination of uric acid in milk. The method is based on an enzymatic-fluorometric technique that requires minimal pre-treatment of milk samples. The present determination of uric acid is based on the enzymatic oxidation of uric acid to 5-hydroxyisourate via uricase where the liberated hydrogen peroxide reacts with 10-acetyl-3,7-dihydroxyphenoxazine via peroxidase and the fluorescent product, resorufin, is measured fluorometrically. Fresh composite milk samples (n=1,072) were collected from both Jersey (n=38) and Danish Holstein (n=106) cows from one local herd. The average inter- and intra-assay variations were 7·1% and 3·0%, respectively. Percent recovery averaged 103·4, 107·0 and 107·5% for samples spiked with 20, 40 or 60 μmof standard, respectively, with a correlation (r=0·98;P<0·001) observed between the observed and expected uric acid concentrations. A positive correlation (r=0·96;P<0·001) was observed between uric acid concentrations using the present method and a reference assay. Storage at 4°C for 24 h resulted in lower (P<0·01) uric acid concentrations in milk when compared with no storage or samples stored at −18°C for 24 h. Addition of either allopurinol (a xanthine oxidase inhibitor) or dimethylsulfoxide (a solvent for allopurinol) did not affect milk uric acid concentrations (P=0·96) and may indicate that heat treatment before storage and analysis was sufficient to degrade xanthine oxidase activity in milk. No relationship was observed between milk uric acid and milk yield and milk components. Authors recommend a single heat treatment (82°C for 10 min) followed by either an immediate analysis of fresh milk samples or storage at −18°C until further analysis.

MO427SAFE USE OF ALLOPURINOL TO TREAT ACUTE URIC ACID NEPHROPATHY IN PREGNANCY: A CASE REPORT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Fahd Khan ◽  
Aizaz Ali ◽  
Jamie Willows ◽  
Didem Tez
Keyword(s):  
Uric Acid ◽  
Case Report ◽  
Serum Creatinine ◽  
Serum Uric Acid ◽  
Renal Tubules ◽  
Normal Range ◽  
History Of ◽  
Uric Acid Nephropathy ◽  
Acute Uric Acid Nephropathy ◽  
In Pregnancy

Abstract Introduction Acute uric acid nephropathy (UAN) is characterized by acute kidney injury (AKI) due to uric acid crystal precipitation within the distal tubules and collecting ducts. We present a young woman, with a history of hyperuricaemia, who was treated with allopurinol for acute UAN during her first pregnancy. She also continued allopurinol treatment during her second pregnancy for prevention of further acute UAN. To the author’s knowledge, this is the first case report of biopsy-confirmed acute UAN during pregnancy. Case report A 20 year old woman, who was 13 weeks pregnant, was admitted with AKI. Past medical history included chronic kidney disease (CKD) and gout since the age of 17. She had an extensive family history of CKD and gout (without diagnosis, despite genetic testing). She had been on daily allopurinol 300mg, but this was stopped 8 weeks prior by her rheumatology team due to concerns about teratogenicity. At that time serum creatinine was at her baseline of 100 μmol/L (normal range 50-120 μmol/L) and serum uric acid had been 740 μmol/L (normal range 140-360 μmol/L). On admission, she felt well and was euvolemic. Serum creatinine was now 352 μmol/L and her serum uric acid level was 1720 μmol/L, with an elevated urine uric acid to creatinine ratio of 1.1. She underwent renal biopsy, which showed significant deposition of uric acid crystals in the renal tubules, confirming a diagnosis of acute UAN. She was given intravenous fluids. The uncertainties of allopurinol use in pregnancy were discussed with her, and she was restarted on allopurinol 200 mg daily. Over the next 3 weeks, serum uric acid decreased to 470 μmol/L and serum creatinine to 116 μmol/L. She was maintained on allopurinol during her pregnancy and delivered a healthy baby girl. She was advised against further pregnancies due to increased risk of maternal and fetal complications. However, three years later she presented at 15 weeks’ gestation. After a discussion regarding the potential teratogenic effects of allopurinol versus the risk of recurrent severe AKI due to acute UAN if it was again discontinued, she chose to continue allopurinol. The pregnancy proceeded without complication. Her daughters are now 8 and 5 years old. They do not have any congenital malformations, though both have mild to moderate learning difficulties. Discussion Allopurinol is approved for the treatment of hyperuricaemia outside of pregnancy, but given it interrupts purine synthesis there is a biologically plausible concern regarding teratogenicity. However, in our patient with long-standing hyperuricaemia it was the discontinuation of allopurinol that precipitated AKI due to the resultant crystal formation when serum uric acid reached very high levels. Biopsy confirmation of acute UAN was vital in this case, given the possibility of missing an alternative diagnosis and the risks of giving empirical allopurinol therapy. Once the diagnosis for her severe AKI was confirmed, it was clear our patient would benefit from uric acid lowering therapy. Our patient had two healthy girls despite using allopurinol from week 16 in her first pregnancy and throughout her second pregnancy. Unfortunately, both girls have mild to moderate learning needs, though it is unprovable whether allopurinol was causative as no study has followed up long term outcomes after foetal exposure during pregnancy.

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