Bioequivalence and beyond: how to expand routine bioequivalence studies to generate new knowledge

摘要

While the major aim of a bioequivalence study is to provide evidence to support approval or registration of the generic product, the data from such a study can be combined with additional simple data or special pharmacokinetic analysis to generate new hypothesis and knowledge in pharmacokinetics and pharmacogenetics. Based on our experience, the following four aspects of new hypothesis/knowledge can be generated. (1) Developing new pharmacokinetic models: examples-developing new pharmacokinetic models to describe drug plasma concentration-time profiles with erratic or double absorption peaks, and developing a simpler approach such as the use of truncated AUC for bioequivalence assessment of long half-life drugs. (2) Linking pharmacokinetics to pharmacodynamics: example-combining a bioequivalence study of zopiclone with the measurement of the central effect of zopiclone, to establish a pharamcokinetic and pharmacodynamic relationship. (3) Linking pharmacokinetics to pharmacogenetics: example-linking the metabolism of acetaminophen and omeprazole to ethnic differences. (4) Determining intra- individual variability: example-proposing hypothesis for high intra-individual variability observed for lovastatin, glibenclamide and varapamil. As many bioequivalence studies are being carried out by many centers in this country, there are plenty of opportunities to generate new knowledge using the approach as described. Further collaboration of among different bioequivalence study centers can lead to generating more credible knowledge and much collaboration should actively and encouraged.