Pharmacokinetic-Pharmacodynamic Modeling of Electroencephalogram Effect of Imipenem in Rats with Acute Renal Failure

The epileptogenic activity of imipenem was investigated in rats with experimental renal failure induced by uranyl nitrate injection by using electroencephalogram (EEG) recording and a pharmacokinetic-pharmacodynamic model including an effect compartment. Results previously obtained with healthy rats were used to estimate the dose of imipenem required to induce an observable but nonlethal EEG effect on the assumption that only the pharmacokinetic parameters of the model would be affected by renal failure. Good agreement was observed between the predicted and observed effects.