Preclinical modeling of changes in drug kinetics caused by acute renal failure in rats

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.