PHARMACOKINETICS OF ORAL EXTENDED-RELEASE DOSAGE FORMS .1. RELEASE KINETICS, CONCENTRATION, AND ABSORBED FRACTION

In this study, we derive pharmacokinetic models for oral extended-rele ase (OER) drug products with defined in vivo release kinetics (IVRK) a nd a compartmental system. Fitting the model to clinical data, we were able to examine the correlation between released and absorbed fractio ns. Furthermore. we found that absorbed fractions of OER products can be expressed by absorption rate and release duration only. The express ion is unchanged in different compartmental systems with the same IVRK , implying that the IVRK drives the pharmacokinetic system of an OER p roduct. The apparent absorption rate constant of an OER product can be estimated by solving an implicit equation using observed concentratio ns. We also propose a new method for calculating absorbed fractions, w hich is more accurate than Loo-Riegelman method. Ultimately, these met hods may permit optimally designed OER products.