A B S T R A C T To test the hypothesis that in both the liver and renal cortex ofthe fructose-loaded rat, severity of depletion of inorganic phosphate (Pi), and not the magnitude of accumulation of fructose-l-phosphate (F-1-P), determines the severity of the dose-dependent reduction of ATP, we intraperitoneally injected fed rats with fructose, 20 and 40 umol/g, alone, and at the higher load, in combination with (a) sodium phosphate, 20 umol/g, administered shortly beforehand or subsequently or, (b) adenosine, 2 ,umol/g, administered beforehand. The following observations were made: (a) With fructose loading alone, at the higher load, both Pi and total adenine nucleotides (TAN) were reduced by one third in the renal cortex and (as previously observed) by two thirds in the liver; and at either load, the reduction of ATP (and TAN)

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The increase in urate clearance during a six hour period following ingestion of zoxazolamine by healthy non-gouty subjects is roughly proportional to the dose over the range of 25 mg. to 250 mg. The uricosuric activity of zoxazolamine was not affected by concomitant administration of a number of other drugs, but was enhanced by probenecid and by sulfinpyrazone and was diminished by acetazolamide and by small amounts of salicylate.Le augment0 del clearance de urato intra sex horas post le ingestion de zoxazolamina per subjectos non-guttose de sanitate normal es grossiermente proportional a1 dosage intra le area ab 25 usque ad 250 mg. Le activitate uricosuric de zoxazolamina non esseva afficite per le administration concomitante de un numero de altere drogas. 1110 esseva promovite per probenecida e sulfinpyrazona e impedite per acetazolamida e micre quantitates de salicylato.INCE THE REVIEW by Bishop and Talbott in 2953,' both the number S and variety of pharmacologic agents affecting renal transport of urate have been augmented. Among recent additions to the group which increase urate clearance in man are phenylbutazone2~3 and its derivative^,^" ethyl biscoumacetate,8 bishydroxycoumarin,D and zoxazo1amine.l0*l1 It is generally agreed that these compounds, like the older uricosuric agents, salicylate and probenecid, act by interference with renal tubular reabsorption of wate. However, the mechanism of this action, as well as that involved in the process of urate reabsorption itself, is completely unknown.12 Thus far, no explanation is apparent to account for the common effect upon urate excretion produced by this heterogeneous collection of drugs. Comparison of the molecular structures of the uricosuric agents has failed to reveal any functional component shared by the entire groups and the diversity of structures represented has been further increased by the addition of zoxazolamine ( fig. 1). Curioiisly, chlorzoxazone,t a metabolite and analog of zoxazolamine in which the amino group is replaced by a hydroxyl group, has no effect upon urate excretion.11J3Initially, it seemed that a uricosuric property was confined to acidic substances. Indeed, Bums and his associates14 found a definite positive correlation between increasing acidity and uricosuric potency among members of the phenylbutazone series. Yet acidity is apparently not a sine qua non for uricosuric activity, as zoxazolamine is a weak base.

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