A STUDY, BY SIMULTANEOUS CLEARANCE TECHNIQUES, OF SALICYLATE EXCRETION IN MAN. EFFECT OF ALKALINIZATION OF THE URINE BY BICARBONATE ADMINISTRATION; EFFECT OF PROBENECID 1

Abstract

Simultaneous renal clearance studies of salicylate, inulin and p-aminohippurate were carried out in 10 human subjects, and the effect of alkalinization of the urine by concomitant injection of bicarbonate was determined. CIn and CPAH were not consistently affected by infusion of sodium salicylate alone or in combination with sodium bicarbonate. Giving sodium bicarbonate had no influence on the proportion of plasma salicylate which is ultrafiltrable. The "free" salicylate clearance ranged from 8.3 to 62.7 ml/minute, with a mean of 29.7 ml/minute. As the urinary pH rose with infusion of sodium bicarbonate, the salicylate clearance increased to a mean approximately three-fold and the "net" tubular reabsorption of "free" salicylate decreased correspondingly. When the urine pH exceeded 7.5 the salicylate excreted usually exceeded that filtered, implying tubular excretion of "free" salicylate and salicyl conjugates under these circumstances. The effect of probenecid (p-(dipropylsulfamyl)-benzoic acid) on salicylate clearance was studied in four cases. Probenecid caused a mean decline of 33% and 40% in "total" and "free" salicylate/inulin ratios, respectively. The data indicate that renal elimination of administered salicylate is a complex 4-phase process involving filtration at the glomerulus, tubular reabsorption, tubular conjugation and tubular excretion. Extra-renal conjugation and oxidation also occur.