Quantitative investigation on renal handling of drugs in rabbits, dogs, and humans.

A renal clearance method based on a computer analysis after administration of a single dose of drug was developed for measuring the renal handling of several drugs in rabbits, dogs, and humans. Secretion and reabsorption of sulfamethizole, sulfanilamide, cephalexin, and ampicillin in the nephron were analyzed quantitatively using the plasma concentration and the urinary excretion rate of the drugs. The validity of the proposed model was demonstrated. It appears that tubular secretion of sulfamethizole, cephalexin, and ampicillin depend on the active transport system which is described by Michaelis-Menten kinetics; the tubular reabsorption of these drugs is expressed by first-order kinetics. The maximum velocity of renal secretion per unit weight of these drugs was much higher in rabbits than in dogs or humans. Reabsorption showed similar values in dogs and humans. These findings suggest that an analysis of the renal handling of drugs in dogs might provide useful information when considering the appropriate therapeutic dose in humans.