PREDICTION OF THE PHARMACOKINETICS OF CEFODIZIME AND CEFOTETAN IN HUMANS FROM PHARMACOKINETIC PARAMETERS IN ANIMALS

Pharmacokinetic behavior of β-lactam antibiotics (cefodizime and cef otetan) in humans were predicted from the animal data. Total body clearance (CLp) of these drugs in humans (weighing 65—69 kg) were successfully extrapolated from the allometric relationship between the clearance for the unbound drug in plasma and body weight (r=0.954—1.000) with a power of 0.948—0.991 for cefodizime and 0.700—0.756 for cefotetan. We also predicted the volume of distribution at steady state (Vdss), the volume of distribution in the central compartment (V1) and the volume of distribution at β-phase (Vdβ) of these drugs in humans from the observed human plasma unbound fraction, inasmuch as the plasma unbound fraction correlated well (r = 0.913—0.995) with the values of Vdss, V1, and Vdβ among various animal species. Based on these predicted pharmacokinetic parameters, we calculated the plasma concentration profiles of these drugs in humans and found a good agreement between the predicted and observed values. We also report here that the prediction is successful when we consider the plasma protein binding of these drugs. © 1990, The Pharmaceutical Society of Japan. All rights reserved.