PHYSIOLOGICAL PHARMACOKINETIC MODEL FOR CEFTAZIDIME DISPOSITION IN THE RAT AND ITS APPLICATION TO PREDICTION OF PLASMA-CONCENTRATIONS IN HUMANS

A physiological pharmacokinetic model for the disposition of ceftazidi me in the rat was developed. The model is composed of 10 compartments which represent most of the organs and tissues of the body. Ceftazidim e concentration-time profiles in the organs and tissues represented in the model were simulated and compared with the observed concentration -time data after i.v. administration of 5 and 20 mg of antibiotic. The model gave an acceptable description of the observed data. The steady -state volume of distribution and total clearance of ceftazidime in he althy humans predicted from data obtained in the rat (0.211/kg and 113 ml/min, respectively) were similar to the values reported for these p arameters by several authors. The model was scaled to humans by using the tissue volumes and plasma flow rates corresponding to a standard m an, the tissue-to-plasma partition coefficients determined in rats, an d the total plasma clearance of ceftazidime observed in humans. Good p redictions of plasma concentrations of ceftazidime in normal subjects and patients with various degrees of impaired renal function were obta ined.