L. Granero et al., PHYSIOLOGICAL PHARMACOKINETIC MODEL FOR CEFTAZIDIME DISPOSITION IN THE RAT AND ITS APPLICATION TO PREDICTION OF PLASMA-CONCENTRATIONS IN HUMANS, European journal of pharmaceutical sciences, 1(1), 1993, pp. 3-11
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.