THE ACCUMULATION OF CHLOROTHIAZIDE AND RELATED SALURETIC AGENTS BY ISOLATED RENAL TUBULES

¹ Merck Institute for Therapeutic Research, West Point, Pennsylvania

The uptake by isolated rabbit renal tubules of four benzothiadiazines of widely varying saluretic activities was studied under a variety of conditions. In Krebs-Ringer bicarbonate buffer, pH 7.4, at 25°C, steady state conditions were attained in each case in 12 to 15 min, with tissue-medium ratios (T/M) varying from 13 for the more polar agents to > 80 for cyclopenthiazide. Both an active component and a passive partition process appear to contribute to the respective uptake of each drug and to the maintenance of concentration gradients between tubule and medium at equilibrium. Decrements in total accumulation in the cold, under nitrogen, and in the presence of inhibitors suggest that active transport contributes equally to the net accumulation of all four drugs. Passive partition, as a function of the respective lipid solubility of each drug, appears to be a major determinant of subsequent distribution among subcellular fractions and, thus, of activity.