Biochemical properties of anti-inflammatory drugs—XII

Whitehouse, M. W.; Kippen, Ian; Klinenberg, James R.

doi:10.1016/0006-2952(71)90435-7

Cited by 33 publications

(2 citation statements)

References 28 publications

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“…These workers proposed, based on earlier work, 12,14,20,42,43,45 that displacement by the drug of fatty acid from albumin was responsible for its principal effects. Greenspan and associates 18 compared the effects of halofenate and clofibrate on lipid synthesis in isolated rat adipocytes and found these drugs to inhibit the incorporation of tagged glucose and pyruvate into adipose fatty acids.…”

Section: Discussionmentioning

confidence: 99%

Effects of halofenate and probenecid on serum lipids and uric acid in hyperlipidemic, hyperuricemic adults

Bassett

Mikkelsen

Buckingham

et al. 1977

Clin Pharma and Therapeutics

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The effect of halofenate was compared with that of probenecid in overweight patients with hyperlipidemia and hyperuricemia. Halofenate induced a prompt and sustained lowering ( 12.7%) of serum triglycerides, but probenecid induced no change in serum triglycerides.Both drugs promptly induced reductions (32%) of serum uric acid. Halofenate induced a 13.3 % increase in serum lactic dehydrogenase. Both drugs induced mild but significant decreases in hemoglobin and in serum albumin, but the between-group differences were not significant. When the effects of the two drugs were divided into subgroups below and above the baseline median value for serum triglycerides, cholesterol, uric acid, and percent ideal body weight, a differential effect on serum triglycerides was noted when serum uric acid and percent ideal body weight were taken as the segregating variables. There was a greater serum triglyceride decline after halofenate in the high-weight group than in the lower-weight group (-25.5% vs +2.7%), and a greater serum triglyceride decline in the high uric acid group than in the lower uric acid group (-22 .6% vs -2.4%). The divergent behavior in regard to initial percent ideal body weight and uric acid level may account for the greater halofenate-induced reductions in serum triglycerides reported by others. In the halofenate group, there was a significant correlation between percent change in triglycerides and percent calories from alcohol. Further study of these responses may provide increased understanding of halofenate action and of the pathogenesis of some types of hyperlipidemia.Halofenate, 2-aceto amidoethyl (p-chlorophenyl) (m-triftuoromethylphenoxy) acetate, is an investigational hypoJipidemic drug which has also been demonstrated to be an effective uricosuric agent. Our study was designed to compare the effects of halofenate and probenecid on serum lipid and uric acid values and on certain monitoring parameters in adults with hyperlipidemia and uricemia. We also sought to determine whether halofenate and probenecid induced different responses in serum cholesterol, triglycerides and uric acid in

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Section: Discussionmentioning

confidence: 99%

Effects of halofenate and probenecid on serum lipids and uric acid in hyperlipidemic, hyperuricemic adults

Bassett

Mikkelsen

Buckingham

et al. 1977

Clin Pharma and Therapeutics

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“…During the screening of numerous novel compounds for in vitro urate displacing properties, four drugs or their metabolites were identified as potentially useful new uricosurics (5). In short-term clinical trials these four agents (sulfaethylthiadiazole, diflumidone sodium, W-2354, and halofenate) were all clearly uricosuric, lowering serum urate concentrations and significantly increasing the renal clearance of urate (6).…”

Section: (2)mentioning

confidence: 99%

Halofenate

Bluestone

Campion

Klinenberg

1975

Arthritis & Rheumatism

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T h e authors have previously proposed that the in vitro displacement of urate from its albumin binding site by an acidic anion was highly indicative of potential uricosuric activity by that anion when administered to humans (1). T h e original experiments on which this hypothesis was based utilized an equilibrium dialysis method to measure urate binding and a fluorescence-quenching technique to detect displacement of 5-dimethylamino-naphthalene-1-sulfonamide (DNSA) from binding sites on human serum albumin T h e recent development of a continuous ultrafiltration technique for measuring urate binding under more physiologic conditions has permitted a reexamination of urate displacement from serum albumin in vitro by certain drugs (3). T h e displacement of sodium (2). urate by uricosuric agents from binding sites on human serum albumin (HSA) and normal serum was thereby demonstrated under in vitro physiologic conditions (pH 7.4, ionic strength 0.16). At 37OC, 0.5 mM sodium salicylate reduced urate bound to 5 g per 100 ml HSA from 19.6% to 9.7%. At room temperature (22.5OC) 22.6y0 urate was bound to 5 g per 100 ml HSA; this was reduced to 12.3y0 by 0.5 mM salicylate, to 9.2y0 by 0.5 mM phenylbutazone, to 14.67, by 0.2 mM diflumidone, and to 17.9a/, by 0.2 mM sulfaethyladiazole (Figure 1). At 22.5"C pooled normal human serum containing 4.8 g per 100 ml albumin bound 23.5% urate, and comparable displacement by drugs was demonstrated (4).During the screening of numerous novel compounds for in vitro urate displacing properties, four drugs or their metabolites were identified as potentially useful new uricosurics (5). In short-term clinical trials these four agents (sulfaethylthiadiazole, diflumidone sodium, W-2354, and halofenate) were all clearly uricosuric, lowering serum urate concentrations and significantly increasing the renal clearance of urate (6).Halofenate was particularly interesting. It is now widely recognized that many patients with gout have Type IV hyperlipoproteinemia characterized predominantly by elevated serum triglyceride concentrations (7). Moreover this association is only partly explained by concomitant obesity or heavy alcohol

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Effect of single oral doses of benzbromarone on serum and urinary uric acid

Jain

Ryan

et al. 1974

Arthritis & Rheumatism

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The effects of various single oral doses of micronized benzbromarone on serum and urinary uric acid and urinary oxypurines were studied in 5 healthy volunteers and in 5 patients with gout. There was an effective, unequivocal, and dose-related reduction in serum uric acid levels in both groups. The simultaneous increased excretion of urinary uric acid but not of oxypurines suggests the mechanism of effect is uricosuria. The prolonged duration of action up to 48 hours after dosing is advantageous as the drug need be taken only once a day. The data presented favor a protracted trial of benrbromarone in patients with gout and hyperuricemia.

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Biochemical properties of anti-inflammatory drugs—XII

Cited by 33 publications

References 28 publications

Effects of halofenate and probenecid on serum lipids and uric acid in hyperlipidemic, hyperuricemic adults

Effects of halofenate and probenecid on serum lipids and uric acid in hyperlipidemic, hyperuricemic adults

Halofenate

Effect of single oral doses of benzbromarone on serum and urinary uric acid

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