Application of a population pharmacokinetic modeling to bioavailability/bioequivalence study of cefadroxil preparations

Abstract

The bioavailability of cefadroxil after administration of two immediate-release preparations, Cedrox and Duricef, to 12 healthy volunteers was studied. Bioequivalence of the preparations was assessed using model-independent parameters and a non-parametric confidence interval method. No difference in the extent of bioavailability and in the absorption rate was detected. However, after applying pharmacokinetic models and a population approach to estimate their parameters, significant differences in absorption kinetics were evident. A one-compartment model with a time lag and two consecutive first-order absorption steps were found to be consistent with the data, and the first step absorption rate constant was greater in the case of Cedrox while in the second step Duricef demonstrated more rapid absorption. No significant differences in the absorption time lag were found. Despite the fact that the difference in the absorption kinetics of cefadroxil for these two formulations is clinically insignificant, the study clearly demonstrated the usefulness of a population approach in determining the intimate details of the drug absorption process.