CONCENTRATION-DEPENDENT TUBULAR SECRETION OF ACETAZOLAMIDE AND ITS INHIBITION BY SALICYLIC-ACID IN THE ISOLATED-PERFUSED RAT-KIDNEY

An isolated perfused rat kidney (IPK) technique was used to study the effect of salicylic acid (SA) on the excretion of acetazolamide (AZ), Initial experiments were conducted in the absence of interactants at t hree nominal AZ concentrations (50, 100, and 250 mu g/ml). Over the co ncentration range studied, AZ demonstrated net tubular secretion in th e IPK, Significant decreases in excretion ratio (4.97 +/- 0.79-2.66 +/ - 1.1) and secretory clearance (0.809 +/- 0.23-0.541 +/- 0.28) were ob served with increasing AZ concentration, consistent with saturation of tubular secretion, Using a facilitated model for renal secretion, val ues of tubular transport parameters were obtained from a plot of excre tion ratio vs. unbound AZ concentration: t(max) = 118 +/- 29.4 mu g/mi n, K-M = 53.4 +/- 22.4 mu g/ml, and t(max(A)) = 6.31 +/- 2.82 mu g/min , In the presence of SA (200 mu g/ml), renal secretion of AZ was inhib ited, as demonstrated by significant decreases in renal clearance (0.7 31 +/- 0.21-0.147 +/- 0.03) and excretion ratio (3.77 +/- 0.82-0.378 /- 0.07). Although these findings were indicative of a reabsorption co mponent to AZ excretion in the IPK that had not been previously propos ed, the results were consistent with a previous investigation of conco mitant administration of AZ and SA in humans (Br. J. Clin, Pharmacol. 27, 866, 1989), thereby endorsing utilization of the IPK as a screenin g tool for renal clearance mechanisms in humans.