1.A model-based meta-analysis to compare urate-lowering response rate of febuxostat and allopurinol in gout patient.
Yi SUN ; Liang LI ; Tian-Yan ZHOU ; Wei LU
Acta Pharmaceutica Sinica 2014;49(12):1674-1683
This study aims to compare the urate-lowering response rate of febuxostat and allopurinol in gout patient using a model-based meta-analysis. The literature search identified 22 clinical trials of gout with a total of 43 unique treatment arms that met our inclusion criteria, and a total of 6 365 gout patients were included in the study. The response rates of allopuriol and febuxostat were characterized by Tmax model and Emax model respectively, and the effect of baseline serum uric acid (sUA) and patient type on the drug effect was tested. The results showed that allopurinol can reach an average maximum response rate of 50.8% while febuxostat can reach a 100% response rate within a very short time, and the ED50 was 34.3 mg. Covariate analysis revealed that baseline sUA has a negative effect on response rate of allopurinol, and a positive effect on the predicted ED50 of febuxostat. For patients who had shown inadequate response to prior allopurinol treatment, the average response rate was about half that of the allopurinol responder patients.
Allopurinol
;
therapeutic use
;
Febuxostat
;
Gout
;
blood
;
drug therapy
;
Gout Suppressants
;
therapeutic use
;
Humans
;
Thiazoles
;
therapeutic use
;
Uric Acid
;
blood
2.Effect of Fenofibrate in Combination with Urate Lowering Agents in Patients with Gout.
You Hyun LEE ; Chan Hee LEE ; Jisoo LEE
The Korean Journal of Internal Medicine 2006;21(2):89-93
BACKGROUND: To assess the efficacy of fenofibrate treatment in combination with urate lowering agents in patients with gout. METHODS: Fourteen male patients with chronic tophaceous or recurrent acute attacks of gout were evaluated in an open-label pilot study of the hypolipidemic agent, fenofibrate (Lipidil Supra(R) 160 mg/d). Patients were stable on urate lowering agents (allopurinol or benzbromarone) for > or =three months without acute attack for the most recent one month before participating. All patients were being treated with established doses of urate lowering agents without modification throughout the study. Clinical and biochemical assessments including serum uric acid, creatinine, liver function test and fasting serum lipid were measured at (1) baseline (2) after two months of fenofibrate treatment and (3) two months after fenofibrate was withdrawn. RESULTS: Serum uric acid was lowered by 23% after two months of fenofibrate treatment (6.93+/-2.16 vs. 5.22+/-1.16 mg/dL; p=0.016). Triglyceride levels were also reduced after fenofibrate treatment (p=0.001). However, this effect was reversed after the withdrawal (p=0.002) of the drug. Alkaline phosphatase was reduced after fenofibrate treatment (p=0.006), but increased 21% after the withdrawal of the drug (p=0.002). By contrast, serum levels of high density lipoprotein and creatinine were increased 9% (p=0.018) and 12% (p=0.006), respectively; however, both levels were significantly decreased to the baseline levels upon withdrawal of fenofibrate. CONCLUSIONS: Fenofibrate can effectively reduce uric acid levels in addition to its known hypolipidemic effect. Fenofibrate may be used as a potential urate lowering agent in patients with gout, especially in those with coexisting hyperlipidemia.
Uricosuric Agents/*administration & dosage
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Uric Acid/blood
;
Procetofen/*administration & dosage
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Middle Aged
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Male
;
Lipids/blood
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Humans
;
Gout/blood/*drug therapy
;
Aged
;
Adult
3.Four-Week Effects of Allopurinol and Febuxostat Treatments on Blood Pressure and Serum Creatinine Level in Gouty Men.
Hyun Ah KIM ; Young Il SEO ; Yeong W SONG
Journal of Korean Medical Science 2014;29(8):1077-1081
The aim of this study was to observe the effects of uric acid lowering therapy (UALT), febuxostat and allopurinol, on blood pressure (BP) and serum creatinine level. Post-hoc data were derived from a phase-III, randomised, double-blind, 4-week trial of male gouty patients that compared the safety and efficacy of febuxostat and allopurinol in adults with gout. The subjects were randomly assigned to one of five groups, 35-37 in each group (febuxostat: 40, 80, 120 mg/d; allopurinol: 300 mg/d; control group: placebo). Blood pressure and serum creatinine level were measured at baseline and at weeks 2 and 4. Diastolic BP and creatinine level had decreased significantly in the UALT groups compared to the control group at week 4. Diastolic BP had decreased significantly in the allopurinol group and serum creatinine level had decreased significantly in the febuxostat groups at week 4. After adjusting for confounding variables, serum uric acid changes were found to be significantly correlated with changes in serum creatinine level but were not associated with changes in systolic or diastolic BP. UALT in gouty subjects significantly decreased diastolic BP and serum creatinine level. Changes in uric acid were significantly correlated with those in serum creatinine level, suggesting the feasibility of renal function improvement through UALT in gouty men.
Allopurinol/*administration & dosage
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Biological Markers/blood
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Blood Pressure/*drug effects
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Creatinine/*blood
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Dose-Response Relationship, Drug
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Gout/*drug therapy
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Gout Suppressants/administration & dosage
;
Humans
;
Hypertension, Renal/diagnosis/etiology/*prevention & control
;
Male
;
Middle Aged
;
Reproducibility of Results
;
Sensitivity and Specificity
;
Thiazoles/*administration & dosage
;
Treatment Outcome
4.Seasonality of Gout in Korea: A Multicenter Study.
Hyo Jin CHOI ; Chan Hee LEE ; Joo Hyun LEE ; Bo Young YOON ; Hyoun Ah KIM ; Chang Hee SUH ; Sang Tae CHOI ; Jung Soo SONG ; Hoyeon JOO ; Sung Jae CHOI ; Ji Soo LEE ; Kichul SHIN ; Jae Bum JUN ; Han Joo BAEK
Journal of Korean Medical Science 2015;30(3):240-244
The object of this study was to evaluate the seasonality of gout in Korea. We retrospectively examined data from 330 patients seen at nine rheumatology clinics, treated with urate lowering therapy (ULT) more than one year after stopping prophylactic medication. Demographic data, clinical and laboratory features, and seasonality of gout onset and flares were collected. Season was classified in three-month intervals. The mean age was 52.2 yr and mean disease duration was 26.8 months. The male to female count was 318:12. The onset of acute gouty attacks was obtained in 256 patients. Gout developed most commonly in summer season (36.7%) (P<0.001) and in June (15.6%, P=0.002). During ULT, there were 147 (male 97.3%) gout flares. Although there was no statistically significant difference, gout flares were more common in summer (30.6%). Aggravating factors were identified in 57 flares: alcohol (72.0%) was most common. In the patients who attained target serum uric acid (<6 mg/dL) at the end of prophylaxis, gout flares were high in fall (35.8%) and September (17.0%). In Korea, the summer is most common season of gout onset and there is a tendency for gout flares to increase during ULT in summer/fall season.
Alcohol Drinking
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Arthritis, Gouty/drug therapy/*epidemiology
;
Blood Pressure
;
Body Mass Index
;
Comorbidity
;
Female
;
Gout Suppressants/therapeutic use
;
Humans
;
Lipids/blood
;
Male
;
Middle Aged
;
Proteinuria
;
Republic of Korea/epidemiology
;
Retrospective Studies
;
*Seasons
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*Symptom Flare Up
;
Uric Acid/blood
5.The unwelcome visitor.
Gim Gee TENG ; Chung Yan TONG ; Choon How HOW ; Lay Hoon GOH
Singapore medical journal 2012;53(8):508-quiz 512
Gout is a chronic, progressive inflammatory disease with intermittent arthritic flares, which should not be regarded as a minor inconvenience or nuisance. It can be effectively controlled when the patient's serum urate level is reduced to less than 360 μmol/l (6 mg/dL) by consistent use of urate-lowering pharmacotherapy. Colchicine prophylaxis for gouty flares during titration of urate-lowering therapy has been underused. Holistic long-term management of gout must encompass patient education, evidence-based dietary advice, screening and aggressive treatment of comorbidities such as hypertension, diabetes mellitus, dyslipidaemia and renal impairment. Acute therapies for recurrent attacks with non-steroidal anti-inflammatory drugs, colchicine and/or corticosteroids should be used judiciously, especially in the elderly, due to the risk of toxicities. With appreciation of the underlying pathogenesis and artful use of the limited drug options, control of gout can be effectively achieved, bringing tremendous satisfaction to the patient and doctor.
Adrenal Cortex Hormones
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therapeutic use
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Adult
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Anti-Inflammatory Agents, Non-Steroidal
;
therapeutic use
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Chronic Disease
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Colchicine
;
therapeutic use
;
Gout
;
diagnosis
;
diet therapy
;
drug therapy
;
Humans
;
Male
;
Uric Acid
;
blood
6.Clinical effect and action mechanism of Weicao Capsule in treating gout.
En-feng SONG ; Qiong XIANG ; Kai-ming REN ; Jia-cai HU ; Fan WU ; Mei-fang GONG ; Hong ZHANG ; Hui-min BI
Chinese journal of integrative medicine 2008;14(2):103-106
OBJECTIVETo study the therapeutic effect of Weicao Capsule (WCC) on gout.
METHODSTwo hundred gout patients were assigned to two groups. The treated group was treated with WCC and the control group was treated with Tongfengding Capsule. Both groups were given the respective treatments orally 3 times a day, 2 capsules each time with 2 weeks as one course and all patients received 2 successive courses of treatment. Changes of blood beta(2)-microglobulin (beta(2)-M), hemoglobin (Hb), 24 h urinary protein (24 h UP), pH value of urine and blood uric acid (BUA) as well as kidney function were observed.
RESULTSAfter treatment, level of beta(2)-M got lowered significantly, Hb and 24 h UP, blood urea nitrogen, serum creatinine and the clearance rate of creatinine, as well as blood lipids all improved obviously in the treated group (all P<0.01), while these parameters remained unchanged in the control group (P>0.05). The pH value of urine was improved in both groups showing an insignificant difference between them (P>0.05). BUA was decreased in both groups with a decrease to a larger extent in the treated group (P<0.01). The total effective rate was 87% in the treated group, which was superior to that in the control group (62%, P<0.05).
CONCLUSIONWCC has a favorable therapeutic effect on gout and its mechanism of action for improving renal function and reducing urinary protein could be related with the lowering of blood beta(2)-M, BUA and lipids.
Adult ; Aged ; Capsules ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Gout ; blood ; drug therapy ; physiopathology ; Hemoglobins ; analysis ; Humans ; Hydrogen-Ion Concentration ; Kidney Function Tests ; Lipids ; blood ; Male ; Middle Aged ; Proteins ; analysis ; Treatment Outcome ; Uric Acid ; blood ; beta 2-Microglobulin ; blood
7.Effect of total saponin of Dioscorea on chronic hyperuricemia and expression of URAT1 in rats.
Guang-Liang CHEN ; Li-Ran ZHU ; Sha NA ; Li LI
China Journal of Chinese Materia Medica 2013;38(14):2348-2353
OBJECTIVETo study the preventive and therapeutic effects of total saponin of Dioscorea (TSD) on chronic hyperuricemia, and its effect on urate transporter 1 (URAT1) in rats.
METHODNinety male rats were randomly divided into 6 groups: the normal group, the model group, TSD high-, medium- and low-dose (300, 100, 30 mg x kg(-1)) groups and the benzbromarone (10 mg x kg(-1)) group. Potassium oxonate and ethambutol were adopted to establish the chronic hyperuricemia model Since the third week, all the rats were intragastrically administered with drugs for 4 weeks, once a day, in order to determine their uric acid in serum and urine, uric acid excretion and xanthine oxidase (XOD). URAT1 mRNA and URAT1 protein expression in rat renal tubular cells were determined by RT-PCR and immunohistochemistry method respectively.
RESULTSerum uric acid level of the model group increased significantly, while uric acid excretion decreased, with high expressions of renal URAT1 mRNA and URAT1 protein. TSD could dose-dependently reduce the serum uric acid level of chronic hyperuricemia rats, increase the concentration of uric acid and uric acid excretion in urine, and reduce renal URAT1 mRNA and URAT1 protein expression. Its effects were similar with that of benzbromarone, but with no significant effect on XOD and urinary volume of chronic hyperuricemia rats.
CONCLUSIONTSD has an obvious effect of anti-hyperuricemia It may reduce the reabsorption of uric acid by inhibiting the high expression of rat renal URAT1.
Animals ; Anion Transport Proteins ; biosynthesis ; genetics ; metabolism ; Benzbromarone ; pharmacology ; Dioscorea ; chemistry ; Gout Suppressants ; chemistry ; pharmacology ; Hyperuricemia ; blood ; drug therapy ; genetics ; urine ; Kidney Tubules ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Saponins ; chemistry ; pharmacokinetics ; pharmacology ; Uric Acid ; blood ; urine ; Xanthine Oxidase ; metabolism
8.Evaluation of penile hemodynamic status and adjustment of treatment alternatives in Peyronie's disease.
Tibet ERDOGRU ; Murat SAVAS ; Namik YILMAZ ; Mustafa Faruk USTA ; Turker KOKSAL ; Mutlu ATES ; Mehmet BAYKARA
Asian Journal of Andrology 2002;4(3):187-190
AIMErectile dysfunction may be observed in up to 80% of patients with Peyronie's disease. An objective evaluation of the erectile function is attempted to work out in patients with Peyronie's disease.
METHODSPenile deformity, sexual function and penile vascular status were analyzed in 123 patients with Peyronie's disease, who had not received any pertinent treatment.
RESULTSPenile deformity, palpable plaque and pain on erection were seen in 112 (91%), 97 (78.8%) and 27 (21.9%) of the 123 patients, respectively. Of the 76 patients evaluated by color Doppler ultrasounography, veno-occlusive dysfunction as the vascular component for erectile dysfunction was found in 17 (22.3%), arterial insufficiency in 10 (13.1%) and a mixed picture in 23 (30.2%).
CONCLUSIONThe documentation of penile erectile function and the determination of the vascular status using color Doppler ultrasonography can guide the appropriate therapeutic choice.
Adult ; Aged ; Antioxidants ; therapeutic use ; Colchicine ; therapeutic use ; Erectile Dysfunction ; diagnostic imaging ; drug therapy ; physiopathology ; Gout Suppressants ; therapeutic use ; Humans ; Male ; Middle Aged ; Penile Induration ; diagnostic imaging ; drug therapy ; physiopathology ; Penis ; blood supply ; pathology ; physiopathology ; Ultrasonography, Doppler, Color ; Vitamin E ; therapeutic use
9.Prevention of Comorbidity and Acute Attack of Gout by Uric Acid Lowering Therapy.
Kowoon JOO ; Seong Ryul KWON ; Mie Jin LIM ; Kyong Hee JUNG ; Hoyeon JOO ; Won PARK
Journal of Korean Medical Science 2014;29(5):657-661
The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA> or =6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.
Adult
;
Allopurinol/therapeutic use
;
Antimetabolites/therapeutic use
;
Benzbromarone/therapeutic use
;
Cardiovascular Diseases/epidemiology/prevention & control
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Comorbidity
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Diabetes Mellitus, Type 2/epidemiology/prevention & control
;
Enzyme Inhibitors/therapeutic use
;
Female
;
Gout/*drug therapy/*prevention & control
;
Gout Suppressants/*therapeutic use
;
Humans
;
Hypertension/epidemiology/prevention & control
;
Male
;
Middle Aged
;
Renal Insufficiency, Chronic/epidemiology/prevention & control
;
Retrospective Studies
;
Thiazoles/therapeutic use
;
Uric Acid/*blood/metabolism
;
Uricosuric Agents/therapeutic use
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Urolithiasis/epidemiology/prevention & control