Effect and safety of Liqing granules in assisting to reduce serum uric acid in rats / 上海预防医学

ObjectiveTo establish a rat model of hyperuricemia （HUA）， to study the effect of Liqing granules on lowering serum uric acid， and to evaluate its safety . MethodsMale SD rats were randomly divided into solvent control group and model group according to their body weight. For the model group， serum uric acid （SUA） was determined after 7 days of intra-gastric administration of potassium oxyazinate. The model group were randomly divided into model control group， positive control group， and low， medium， high dose group based on SUA level. Each group from the model group continued to receive potassium oxyazinate in the morning. The animals in the model groups received 0.5% CMC-Na， 10 mg·kg-1 benzbromarone （Doses by body weight） and Liqing granules 0.6， 1.2， 2.4 g·kg-1 （Doses by body weight）， respectively in the afternoon. 0.5% CMC-Na suspension with the same volume was given both in the morning and afternoon for the solvent control group. Levels of SUA， creatinine （CREA）， alanine aminotransferase （ALT） and aspartate transaminase （AST） were determined after 32 and 45 days administration of the test substance. ResultsSUA of the model group was （218±23） μmol·L-1 after 7 days of modeling， which was significantly higher than that of the solvent control group （P<0.001）. After 32 days administration of the test substance， SUA didn’t significantly decrease in each dose group （P>0.05）. CREA in the medium and high dose groups significantly decreased （P<0.05）. After 45 days administration of the test substance， SUA in each dose group was significantly decreased （P<0.001）， but CREA， ALT， and AST were not significantly different in each dose group in comparison with the model control group （P>0.05）. ConclusionLiqing granules can assist in lowering blood serum uric acid in the rat HUA model， and no damage to liver and kidney function is found.

Effects of CYP2C9*3 Gene Polymorphism on Therapeutic Efficacy of Benzbromarone in Lowering Uric Acid and Its Hepatotoxicity / 中国药房

OBJECTIVE：To study the effects o f CYP2C9*3 gene polymorphism on therapeutic efficacy of benzbromarone in lowering uric acid and its hepatotoxicity. METHODS ：A retrospective study was conducted to analyze the relevant clinical indicators and genotypes of 196 gout patients who received benzbromarone and CYP2C9*3 gene polymorphism test in Wuhan third hospital from Jan. 2018 to Sept. 2019. RESULTS ：Among 196 patients，179，15 and 2 patients with CYP2C9*3 genotypes * 1/*1， *1/*3 and * 3/*3 genotypes were found ，respectively，and the distribution of each genotype was in line with Hardy-Weinberg balance（P＞0.05）. Before treatment ，there were no significant differences in the levels of UA ，Scr，ALT，AST and CRP between *1/*1 genotype and * 1/*3+*3/*3 genotype（P＞0.05）. After 4 weeks of treatment ，the UA ，Scr，CRP levels of patients with * 1/*1 genotype as well as the UA and CRP levels of patients with * 1/*3+*3/*3 genotype were significantly reduced ，the UA level of patients with * 1/*1 genotype was significantly lower than that of patients with * 1/*3+*3/*3 genotype（P＜0.05 or P＜0.01）. The ALT and AST levels had no obvious changes in patients with different genotype before and after treatment ，and they were in the normal range. No serious abnormal liver function was observed during the treatment. CONCLUSIONS ：Therapeutic efficacy of benzbromarone in lowering uric acid in gout patients with CYP2C9*3 genotypes * 1/*1 genotype is better than that of * 1/*3 and * 3/*3 genotypes. However ，the gene polymorphism may be not associated with its hepatotoxicity.

Clinical Observation of Febuxostat in the Treatment of Type 2 Diabetic Nephropathy Complicated with Hyperuricemia / 中国药房

OBJECTIVE: To observe clinical efficacy and safety of febuxostat in the treatment of type 2 diabetic nephropathy complicated with hyperuricemia. METHODS: A total of 137 patients with type 2 diabetic nephropathy complicated with hyperuricemia selected from our hospital during Jan. 2014-Jun. 2016 were divided into group A (46 cases), B (47 cases), C (44 cases) according to random number table. On the basis of routine treatment, group A was given Allopurinol tablets orally with initial dose of 0. 05 g, bid; increasing to 0. 10 g, bid, 2 weeks later. Group B was given Benzbromarone tablets 50 mg orally, qd. Group C was given Febuxostat tablets orally with initial dose of 40 mg, qd; increasing to 80 mg, qd, 2 weeks later. All patients received treatment for consecutive 12 weeks. Clinical efficacies of 2 groups were observed, and the levels of serum uric acid (SUA), Scr and BUN were also observed before and after treatment. The occurrence of ADR was recorded. RESULTS: Four, six, three patients withdrew from the study in group A, B, C, respectively. The total response rates of group B, C (87. 8％, 85. 4％) were significantly higher than that of group A (76. 2％), with statistical significance (P＜0. 05); there was no statistical significance between group B and C (P＞0. 05). Before treatment, there was no statistical significance in the levels of SUA, Scr or BUN among 3 groups (P＞0. 05). Four weeks after treatment, the levels of SUA in 3 groups were decreased significantly compared to before treatment, with statistical significance (P＜0. 05); there was no statistical significance in other indexes among 3 groups or between before and after treatment (P＞0. 05). Twelve weeks after treatment, the levels of SUA in 3 groups were decreased significantly compared to before treatment and 4 weeks after treatment, and group B and C were significantly lower than group A; the levels of Scr in group A and C were decreased significantly compared to before treatment, while that of group B was increased significantly compared to before treatment and group B was significantly higher than group A and C, with statistical significance (P＜0. 05). There was no statistical significance in the levels of Scr or BUN among 3 groups compared to 4 weeks after treatment; there was also no statistical significance in the levels of SUA between group B and C, the levels of Scr between group A and C (P＞0. 05). Total incidence of ADR in group C (12. 20％) was significantly lower than group A and B (25. 58％, 24. 39％), with statistical significance (P＜0. 05); there was no statistical significance between group A and B (P＞0. 05). CONCLUSIONS: Febuxostat is better than allopurinol in reducing the level of SUA in type 2 diabetic nephropathy patients with hyperuricemia. It shows small effect on renal function with better safety.

A Clinical Study of Combined Therapy of Colchicine and Benzbromarone Capsules in the Treatment of Gouty Arthritis at Non-Acute Episode Stage / 昆明医科大学学报

Objective To explore and analyze the clinical values of combined therapy of colchicine and benzbromalone capsules in the treatment of gouty arthritis of non-acute episode. Methods From December 2015 to February 2017, 60 patients with gouty arthritis who were not in acute attack were randomly divided into the combined group and the control group, with 30 cases in each group. The control group was given benzbromarone capsules and the combined group was given colchicine combined with benzbromarone capsules. The changes of laboratory indexes [blood uric acid, erythrocyte sedimentation rate (ESR),C reactive protein (CRP),alanine aminotransferase (ALT), glomerular filtration rate (GFR) ], and clinical symptoms (pain, lesion joint limitation, fever, redness and tenderness) were measured and compared in the two groups before and after the treatment. The daily living ability scale (SF-36) was used to evaluate the quality of daily life before and after the treatment, and the incidence rate of drug adverse reactions during the treatment was also counted. Results No significant differences were found in the laboratory related indexes, clinical symptoms and quality of life before the treatment between the two groups (P＞0.05) . After the treatment, the levels of ALT and GFR were not significantly fluctuated in the two groups, but the levels of blood uric acid, ESR, CRP, pain symptoms and quality of life were improved, and the increasing degree in the combined group was more significant than that of the control group. and the number of episodes of acute gouty arthritis in the combined group was also lower than that in the control group, and the difference between the above indexes was statistically significant (P＜0.05) . The total incidence rate of adverse reactions was 30% in the combined group, which was not significantly different from that in the control group with 26.67% (χ2=0.180,P=0.857) . Conclusions The use of colchicine combined with benzbromalone capsules is as the safe as the single use of benzbromalone capsules and the effect of the former one is better than that of the latter one in the treatment of gouty arthritis at non-acute episode stage.

Clinical study ofHuangkui capsule combined with benzbromarone on the treatment of the patients with chronic uric acid nephropathy / 国际中医中药杂志

Objective To observe the clinical effect ofHuangkui capsule combined with benzbromarone on the treatment of the patients with chronic uric acid nephropathy (CUAN).Methods A total of 60 patients were recruited and divided into the treatment group and the control group by using the random number table method, each group 30 patients. Two groups were treated with conventional treatment, such as low purine, low protein diet, quit smoking and drinking extra water. The control group was added with oral benzbromarone, and the treatment group was added with oralHuangkui capsule. All the treatments last 8 weeks. Theblood uric acid (BUA), serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (Cys-C), SOD, 24-hour urinary protein quantity and Urinary sediment red blood cell count were detected by the automatic biochemical analyser.The clinical effect was evaluated by the Rheumatoid arthritis (RA) quality of life questionnaire.Results Compared with the control group, the total effective rate in the treatment group was 86.64% (26/30), which was significantly higher than that of 63.33% (19/30) in the control group (χ2=7.264, P=0.001). After treatment, the BUA (273.52 ± 110.37μmol/Lvs. 331.28 ± 126.54μmol/L,Z=-2.543), BUN (6.24 ± 1.23 mol/Lvs. 8.16 ± 2.35 mol/L,Z=-2.680), SCr (90.37 ± 20.16μmol/Lvs. 110.38 ± 16.72μmol/L,Z=-2.534), Cys C (0.86 ± 0.51 vs. 1.03 ± 0.10,Z=-2.372) in the treatment group were lower than those of the control group (P<0.01); SOD (156.37 ± 32.04μmol/Lvs. 43.36 ± 31.52μmol/L,Z=-2.041) in the treatment group was higher than that in the control group (P<0.01); the 24 hours urinary protein (439.86 ± 250.41 mg/24hvs.897.69 ± 213.37 mg/24h,Z=-2.853), urine sediment RBC counts (50.31 ± 14.06 points/μlvs.213.47 ± 38.46 points/μl, Z=-2.106) in the treatment group were lower than those in the control group (P<0.01); the physiological function(43.14 ± 2.06 pointsvs.36.48 ± 3.21 points,Z=10.362), the psychological function (40.76 ± 3.28 points vs. 16.54 ± 3.71 points,Z=9.547), social function (40.74 ± 3.58 points vs. 33.04 ± 5.48 points,Z=6.034), healthy self-awareness (24.57 ± 1.97 points vs. 22.63 ± 3.43 points,Z=4.236) and total score (127.38 ± 6.43 points vs. 107.69 ± 13.57 points,Z=6.754) in the treatment group were higher than those in the control group (P<0.01) . Conclusions TheHuangkui capsule combined with benzbromarone could reduce CUAN patient's blood uric acid levels, protect renal function, and improve the quality of life.

Acute Tubular Necrosis in a Kidney Transplant Patient Using Benzbromarone: A Case Report / 대한이식학회지

Benzbromarone is a uricosuric agent for hyperuricemia and gout. Some of its well-known side effects include hypersensitivity, renal calculi, and gastrointestinal problems. Although the drug was withdrawn from U.S. market due to severe hepatotoxicity, it is still available in some countries including Korea. We describe a 19-year-old male who was admitted with general weakness and azotemia after use of benzbromarone. A kidney biopsy revealed acute tubular necrosis without an evidence of urate nephropathy. After discontinuation of benzbromarone, the renal function returned to baseline. This is the first case of acute tubular necrosis associated with benzbromarone use.

The Effect of Low Dose Aspirin on Serum and Urinary Uric Acid Level in Gouty Arthritis Patients / 대한류마티스학회지

OBJECTIVE: To investigate the effect of low dose aspirin on serum and urinary uric acid level in gouty arthritis patients. METHODS: 22 male gouty arthritis patients (12 treated with allopurinol and 10 with benzbromarone) were enrolled in a prospective study. Mean age (+/-SD) was 57.3+/-10.4 years. Patients had been treated with hypouricemic agent for at least 3 months. Low dose of aspirin (100 mg/ day) were administered for 4 weeks. During the study period, hypouricemic agents were remained on the same dosage. Demographic data were collected at baseline. Laboratory tests including serum uric acid, blood urea nitrogen, creatinine, 24 hours urine uric acid, creatinine clearance (Ccr), and 24 hours urine urea nitrogen were measured at baseline and then every 4 weeks for 12 weeks. RESULTS: At baseline, there was no difference in age, serum uric acid, 24 hours urine uric acid, Ccr and 24 hours urine urea nitrogen between allopurinol and benzbromarone groups. After aspirin treatment, levels of serum uric acid (p=0.901 by paired t-test in allopurinol group, p=0.617 in benzbromarone group), 24 hours urine uric acid (p=0.789, p=0.410), Ccr (p=0.480, p=0.219), 24 hours urine urea nitrogen (p=0.284, p=0.250) did not change significantly at 0 and 4 weeks. Acute gouty attack did not occur during the study period. CONCLUSION: Low dose aspirin does not influence serum uric acid level or urinary uric acid excretion in gouty arthritis patients treated with allopurinol or benzbromarone.

Analysis of Marketing and Clinical Application Tendency of Antipodagrics in China / 中国药房

OBJECTIVE:To analyze the market tendency and the overall marketing situation in clinical application of antipodagrics in hospitals of China.METHODS:The analysis was performed with the help of the parameters obtained from domestic authoritative medical economy information network.RESULTS&CONCLUSIONS:The competition for the pro?duction and the marketing of benzbromarone is fierce,yet its antipodagric effect and market prospect are generally considered to be good,manufactories of colchicine and allopurinol remain unchanged and the competition for these products is mild.An?tipodagrics market is expected to be further expanded.

Study on Effect of Benzbromarone in the Patients with Gout / 대한류마티스학회지

OBJECTIVE: Benzbromarone is a most potent uricosuric agent which has been marketed in Europe. The purpose of this study was to evaluate the safety and efficacy of benzbromarone as a uric acid lowering agent in gouty patients in Korea. METHOD: Twenty-one patients with gout, who were lower excreter of uric acid and had no other complication of gout, were treated with benzbromarone for 6 months. In these patients we checked complete blood count, liver function test, BUN, creatinine, serum uric acid, 24 hour urine uric acid excretion and uric acid clearance before and after treatment with benzbromarone. RESULTS: Significant improvements(p<0.01) were found in the serum uric acid level, 24h uric acid excretion and uric acid clearance. The mean serum uric acid decreased from 8.2mg/dl to 5.1mg/dl at the end of 6 months; mean urinary uric acid excretion increased from 425.9mg/day to 760.3mg/day; and the uric acid clearance increased from 3.5mL/min to 10.9mL/min. There are no clinical or laboratory side effects, except skin rash in the one patient. CONCLUSION: Benzbromarone was effective to control plasma uric acid concentration at doses ranging from 25 to 50mg/day.