APPLICATION OF A POPULATION PHARMACOKINETIC MODELING TO BIOAVAILABILITY BIOEQUIVALENCE STUDY OF CEFADROXIL PREPARATIONS

The bioavailability of cefadroxil after administration of two immediat e-release preparations, Cedrox and Duricef, to 12 healthy volunteers w as studied. Bioequivalence of the preparations was assessed using mode l-independent parameters and a non-parametric confidence interval meth od. No difference in the extent of bioavailability and in the absorpti on rate was detected. However, after applying pharmacokinetic models a nd a population approach to estimate their parameters, significant dif ferences 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 ra te constant was greater in the case of Cedrox while in the second step Duricef demonstrated more rapid absorption. No significant difference s in the absorption time lag-were found. Despite the fact that the dif ference in the absorption kinetics of cefadroxil for these two formula tions is clinically insignificant, the study clearly demonstrated the usefulness of a population approach in determining the intimate detail s of the drug absorption process.