Renal excretion of hypoxanthine and xanthine in primary gout (original) (raw)
1988, The American Journal of Medicine
The renal excretion of uric acid is usually diminished in primary gout with respect to increased serum urate levels. To determine whether the renal excretion of uric acid precursors, hypoxanthine and xanthine, is also abnormal in primary gout, the concentrations of these purines were measured in plasma and 24-hour urine samples in normal subjects, in patients with primary gout and uric acid underexcretion, and in patients with enzyme deficiencies that are known to result in overproduction of uric acid. SUBJECTSANDMEI'HODS: Threegroupsofsubjects were studied: Group I consisted of 10 ambulatory healthy normal men; Group II consisted of 15 patients in whom primary gout was diagnosed; and Group III consisted of 10 patients with various enzyme defects lmown to produce an excessive synthesis of uric acid. In each subject, plasma and 24hour urinary uric acid, hypoxanthine, xanthine, and creatinine concentrations were measured and the mean of three consecutive determinations was used. The fractional excretion of puke compounds was calculated from a formula. Hypoxanthine phosphoribosyltransferase, adenine phosphoribosyltransferase, and hemoglobin were also measured in each subject. RESULTS: Plasma hypoxanthine and xanthine were increased in the two groups of patients compared with the control subjects. Urinary hypoxanthine and xanthine levels were reduced in gouty patients compared with control subjects, whereas levels were increased in patients with uric acid overproduction. A positive correlation was found between the renal clearances of uric acid, hypoxanthine, and xanthine. CONCLUSION: The results indicate that the renal excretion of hypoxanthine and xanthine is severely impaired in most patients with primary gout. From the Departments of Internal Medi ci ne and Clinical Biochemistiy. Metabol i c Unit, "
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Metabolism, 1986
Metabolic studies were conducted in 56 patients with primary gout and in ten normal subjects to assess differences in the tubular transport mechanisms of urate. Renal handling of uric acid was examined by means of pyrazinamide and probenecid tests at increased and pharmacologically reduced serum urate concentrations in both groups. Patients with gout showed similar serum urate levels and glomerular filtration rates than controls at both serum urate levles. Pyrazinamide decreased urinary uric acid excretion to less than 1 .O% of the urate filtered load in both groups at increased and diminished serum urate concentrations. The maximum uricosuric response promoted by probenecid at high serum urate levels was (mean + SD) 3,707 + 443 pg/min/l.73 m2 in controls and 2,215 f 738 pg/min/1.73 m2 in patients with gout (P G 0.01 I. Forty-four patients had a daily uric acid excretion rata below 700 mg/1.73 m2, and all of them showed a diminished uricosuric response to probenecid. When serum urate was reduced in normal subjects and 30 patients to a mean of 2.1 and 2.3 mg/dL, respectively, probenecid elicited a significantly lower urate excretion rate in gout (532 + 202 pg/min/l.73 m2) than in controls (922 + 138 Hg/min/l.73 m2; P < 0.01 I. Among these 30 patients examined in their basal state and at decreased serum urate levels, uric acid excretion following probenecid was normal in six and diminished in 24 in both situations. The difference between maximum uricosuria and basal urate excretion was not increased in gouty patients. [2-"C]uric acid kinetics showed a metabolic clearance rate of 6.3 f 1.5 L/24 h/m2 in five gouty normoexcretors and 3.5 + 0.8 L/24 h/m* in three underexcretors (P < 0.01). classified according to both 24hour uric acid excretion and the uricosuric response elicited by probenecid. These data suggest an impaired tubular secretion of urate in most patients with gout that is not normalized by decreasing serum urate levels. The impaired tubular transport of urate may contribute to increased serum urate in primary gout.
The Biochemical & Physiological Implication of Gout
The article focuses on several underlying biochemical features regarding the manifestation of Gout. The high level Uric Acid (UA) built up in circulation is a major indication of the disease which is found only within human and higher apes. In moderate briefing it describes the nature, causes, sexual biasness and de-novo synthesis of UA and its excretion from the body under physiologic condition at the onset of this metabolic disorder. Categorically, the information offered is classified as follows: A. General knowledge about the disease caused due to higher UA / Urate level inside circulating plasma normally termed Hyperuricemia viewed commonly among the Gout sufferers including the role of purine enriched food and excessive alcohol consumption associated with its higher incidence. B. The physico-chemical mechanism of crystal formation and the cause of its deposition in faraway joints. C. The faulty Purine synthesis / metabolism or malfunctioning of Urate excretion through the kidney by various transporters leading to the manifestation of Hyperuricemia or Gout and simultaneously including its versatility, nature, ability and genetic identity. D. The discussion involving enzymatic pathway behind Hyperuricemia viewed within the Gout sufferers in the light of Purine synthesis and metabolism along with the genetic abnormality. E. The non-expression of Uricase gene in human due to nonsense mutation helps exacerbate the accumulation of UA when other enzymatic problem came into effect. AJBBL http://www.ajbbl.com/ Volume 01 Issue 01 2012 F. The immunological problem created by the deposition of Urate crystal due to Hyperuricemia initiating the Gout attack causing pain, swelling and flare ups are elaborated along with their remedies. G. The pharmacological mechanism and the adverse roles of any drugs commonly used during treatment either for the short term or long term purposes in controlling or preventing its future recurrence is also included in this review.
Evaluation of Allopurinol (Xanthine Oxidase Inhibitor) inManagement of Primary Gout (Niqras)
2020
Gout is the most prevalent crystals-induce arthropathy and is associated with impaired health-related quality of life. It is characterized by hyperuricemia and recurrent attacks of acute arthritis, often eventually associated with urate deposits in the tissues which may be manifest as tophi. Several studies suggest that its prevalence and incidence have risen in recent decades. The objective of present trial was to validate and to assess the efficacy and safety of Xanthine-oxidase inhibitor drugAllopurinol on the patients of primary gout. The study was of 18 months and designed as a randomized open-label with a sample size of 30 patients. The progress in subjective parameters was evaluated weekly, and at the baseline, fifteen days and thirty days in objective parameter. On the basis of severity, the subjective parameters were ranked arbitrarily from 03. There was observed a considerable improvement in subjective as well as objective parameters and no undesirable effect during and at...
Clinical pharmacology and therapeutics, 2011
The treatment of gout requires a lowering of serum urate (SU) levels, and allopurinol is the drug that is most commonly used for this purpose. The objectives of this study were to define the relationships between allopurinol dose on the one hand and plasma oxypurinol, renal function, and SU levels on the other and to determine the minimum plasma oxypurinol concentration that would result in a target level of <6 mg/dl (0.36 mmol/l) of SU. For this purpose, 82 patients who had been receiving allopurinol for at least 1 month were recruited. Patients with SU <6 mg/dl were followed up quarterly for 12 months. In patients with SU ≥6 mg/dl, the dose of allopurinol was increased to bring the level of SU to <6 mg/dl. These patients were followed up once a month until the SU level remained at <6 mg/dl for 3 consecutive months; thereafter they were seen quarterly. SU, creatinine, and plasma oxypurinol were measured 6-9 hours after administration of the allopurinol dose. There were ...
Urinary Excretion and Renal Clearance of Allopurinol in Female Gout Patients
Journal of Analytical & Bioanalytical Techniques, 2015
Drugs removed from the body either without changing from its original form or in the form of its metabolite. Allopurinol drug decreases uric acid level in blood and it is used for the treatment of gout and tumor lysis syndrome. Allopurinol and its active metabolite oxipurinol stop the function of xanthine oxidase which forms uric acid from xanthine and hypoxanthine. In this study a quantitative assay using high-performance liquid chromatography (HPLC) with UVdetection was used as a method for quantification of allopurinol and oxipurinol in human serum and urine samples of gout patients after allopurinol administration. The urinary excretion and renal clearance was determined in male gout patients. Blood and urine samples of the human male patients of gout (n=10) after the oral administration of 300mg drug were taken at different time intervals. Results of this study show that there is slow metabolism of allopurinol inside body due to its extensive bonding with blood proteins. Statistical analysis was performed by expressing all the data as mean and ± standard error of mean. The effect of pH and diuresis on renal clearance of allopurinol was studied by regression analysis.
Clinical Effects of Xanthine Oxidase Inhibitors in Hyperuricemic Patients
Medical Principles and Practice, 2020
Highlights • Hyperuricemia is a well-recognized risk factor for gout and has been shown to contribute to vascular damage. • Large long-term clinical trials have demonstrated xanthine oxidase inhibitors to be generally effective, safe, and relatively well-tolerated. • New urate-lowering drugs seem to be particularly efficacious for acute treatment of refractory hyperuricemia, though their use is supported by relatively small clinical evidence.
Combination urate-lowering therapy in the treatment of gout: What is the evidence?
Seminars in Arthritis and Rheumatism, 2018
Background: Combination therapy that includes a uricosuric and xanthine oxidase inhibitor (XOI) is recommended in guidelines for patients with gout who do not meet treatment targets with XOI monotherapy alone. While the use of combination therapies has been investigated for many years, we reviewed data from the published studies to investigate the efficacy and safety of this approach. Methods: Relevant published papers were identified by keyword search on PubMed and categorized according to the types of combination therapies included. Study methods and results were summarized. Outcomes of combination therapy were compared with respective monotherapies, where possible. Results: Efficacy was assessed by changes in serum urate (sUA), urinary uric acid, gout flare rates, and /or tophi. Safety assessments, where reported, included adverse events and, for more recent studies, laboratory assessments. Early studies in the 1960s based on case reports or open-label designs and more recent, well-designed studies with large patient numbers provided consistent outcomes: that combination therapy with a uricosuric and a XOI provides substantially greater sUA lowering than achieved by either monotherapy. Greater sUA lowering translated to greater gout symptom control, including improved tophus resolution. Conclusions: Combination therapy with a uricosuric and an XOI offers additional sUA lowering compared to monotherapy alone and can provide benefit for achieving therapeutic targets in patients with gout who do not achieve target sUA or are intolerant of XOIs at appropriate monotherapy dosing.
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