ABSTRACT
Bioequivalence (BE) testing is based on the assumption that the circulating systemic drug level is predictive of drug clinical effect. In vitro/in vivo correlations should be explored over a specified range of variables using dissolution rate or fraction released vs. absorption rate profile as assessed by deconvolution or statistical moment theory. When single-dose studies suffice for demonstrating BE and when multiple-dose studies are warranted are very important design issues. An issue that has gained prominence in the last few years is the role of active metabolites and stereoisomers. The role of pharmacodynamics in BE is a rapidly evolving arena. The role of animals in understanding toxicology during new drug development has been invaluable. The magnitude of this variability for a particular dosage form must be considered in light of the kinetic-dynamic relationship of drug concentration to response before decisions regarding BE criteria can be devised and established.
