Bioequivalence and Pharmacogenetics
Mukerrem B.Y. Aycan.
The current drug development framework grants the innovator companies the opportunity to market a new drug
exclusively for a defined time period under patent protection. After the patent protection period ends, other companies are
permitted to produce their own generic version provided they meet bioequivalance. Accordingly, the test compound and
the reference compound pharmacokinetic parameters are expected to be within 80% to 125% in terms of Cmax (maximum
plasma concentration) and AUC (area under the curve). Generally, bioequivalence trials are carried out in healthy volunteers
as a crossover, open, two-way, randomized design where each volunteer takes both test and reference medication in different
periods. The remit of a bioequivalence trial is investigating the similarity of test and reference compounds without observing
the pharmacodynamics or therapeutic concentration of the medication. If the trial medication has a bioactive metabolite, in
this case, both the main molecule and bioactive metabolite should demonstrate bioequivalancy in terms of pharmacokinetic
parameters. Both inter- and intra-individual pharmacokinetic variability can be impacted through pharmacogenetic
differences and gene expression regulation at an individual and population level. Surprisingly, pharmacogenetics has been
considered very little in bioequivalence studies. This expert review article aims to initiate a discussion on the ways in
which these two fields of biomedicine offer synergy for innovation, and the ways forward to address the extant challenges
at the unique intersection of pharmacogenetics and bioequivalance research and development.
Keywords: Bioequivalence, bioavailability, clinical trials, gene expression, personalized medicine, pharmacogenetics, polymorphism.
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