THE RENAL CLEARANCE OF BARBITAL AND THE MECHANISM OF ITS REABSORPTION

¹ Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York 32, N. Y.
² Department of Pharmacology, University of Florence, Florence, Italy

The renal clearance of barbital was measured in dogs after doses of 5 to 250 mgm./kgm. During water diuresis the ratio of barbital clearance to filtration rate (C_B/C_CR) was about 0.09 at all dosage levels. The administration of food, saline, or acidifying or alkalinizing salts led to an increase in the clearance of barbital (C_B/C_CR = 0.14). Similar ratios were obtained after a mercurial diuretic or phlorhizin. In all experiments there was an augmentation of the C_B/C_CR ratios with higher urinary flows. In no clearance period was the ratio of urinary to plasma concentration of barbital less than unity, but at high urinary flows the ratio always approached unity. After large doses, barbital causes an increase in the pH of the urine, which cannot be ascribed to inhibition of carbonic anhydrase.

The data support the hypothesis that barbital is reabsorbed in the renal tubules as the free acid by a process of back-diffusion. Various physico-chemical concepts are employed to explain (1) the variations of the clearance ratios in relation to urinary flow and to the excretion of other compounds, (2) the alkalinity of the urine after high doses of barbital, and (3) the difference in renal clearance between barbital and urea, which is also reabsorbed by back-diffusion. The application of the present work to other species and to other barbiturates is discussed.

An improved method for the determination of barbital in plasma and urine is described.