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The rates of total and extrarenal elimination of amikacin, cefoperazone, ceftriaxone, gentamicin, mesocain, theophylline, tobramycin, and polyfructosane-S were determined in rats with intact kidneys and in those after bilateral nephrectomy. While the values of the elimination constants of the tested drugs were markedly higher in the rats than in man, the ratio of nonrenal and total elimination constants, expressing the fraction of drugs eliminated extrarenally, is close to the value found in man. These findings suggest that the model might be useful in preclinical drug testing and can help in the prediction of changes in the kinetics of drugs caused by renal failure.

Ten days after four-fifths nephrectomy in rats (four-fifths of the renal parenchyma removed), the total and renal elimination constants of tobramycin were lowered by one-half. The biological half-life of tobramycin doubled. These results suggest that soon after nephrectomy the residual nephrons are able to increase the rate of excretion of tobramycin. The increase in mass of the remaining renal tissue between day 10 and day 80 after nephrectomy had no effect on the biological half-life, on the total and renal elimination constants, and on the renal clearance of tobramycin. During endotoxin shock and burn shock, concentrations of tobramycin in serum decreased at a slower rate. The highest serum concentrations of tobramycin were observed in rats with shock due to burns.