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The influence of urinary pH on the renal excretion of salicyl derivatives during aspirin therapy.

1950; National Institutes of Health; Volume: 35; Issue: 2 Linguagem: Inglês

William S. Hoffman, Catherine Nobe,

Intramuscular injections and effects

Abstract The validity of the scheme of Smith and associates for the partition analysis of the salicylate fractions in urine has been confirmed. The equations obtained differed only slightly from those of these workers. This analytical method has been utilized to study the effect of sodium bicarbonate administration on the excretion of salicylate during aspirin therapy for acute rheumatic fever. The apparent clearance of free salicylate during regimens of aspirin without added sodium bicarbonate ranged from 0.5 to 9.66 per cent of the corresponding creatinine clearances, but most of the values were below 2 per cent. The true clearances, based on the unbound plasma salicylate concentration, were probably four to five times as high. Even such clearances were of the order of those of chloride, and this implied that the free salicylate filtered through the glomeruli was for the most part reabsorbed by the tubules. The free salicylate constituted about 20 per cent of the total salicylate in the acid urines, the remaining 80 per cent being almost equally divided between salicyluric acid and salicyl glycuronide. When sodium bicarbonate was administered along with the aspirin in quantities sufficient to alkalinize the urine, the free salicylate clearances were increased to three to thirteen times the original values. The clearances were found to be proportional to the urinary pH. This increased excretion of free salicylate made it comprise as much as 70 per cent of the urinary total salicylate, the average being 52 per cent. The total salicylate clearance was thereby also increased as much as 200 per cent. These clearances were also found to be proportional to the urinary pH. The enhanced clearances of total salicylate accounted for the significant drop in plasma salicylate levels, which occurred in all instances. The true clearance of free salicylate in alkaline urines approached that of creatinine. Thus, excess of base prevented almost completely the reabsorption of free salicylate from the glomerular filtrate. Since at the most only traces of conjugated salicylates were present in the plasma, the clearance of these conjugates was either infinitely high or at least as high as p -aminohippurate. Such findings indicated that conjugated salicylates either were produced in the renal tubules or excreted through them, or both. Conjugation of salicylate has for its function a special type of detoxication which converts the ordinarily poorly excretable free salicylate into compounds which are easily excretable.