Bioequivalence and Bioavailability Forum

Dear Essar,

different Genotypes (coded in the individual Genome) express different forms (polymorphism) of proteins e.g., metabolizing liver enzymes (CYP450) and transporters (PGP). Individuals showing different forms are called Phenotypes.
For some drugs being metabolized we see different genotypes in the population (e.g., fast/extensive [aka EM] and slow/poor metabolizers [aka PM]).

In the general BE-setting this is of no interest, since the phenotype does not change (a poor metabolizer shows high concentrations both for test and reference, and a fast metabolizer low conc's...)

If your drug shows such a pattern (generally you notice it by a large inter-individual CV and ratio of >10 of the highest/lowest AUCs), two points are of interest:
If you plan a cross-over multiple dose study for such a drug, you may consider phenotyping in screening for safety reasons (i.e., include only FMs; otherwise you will end up in toxic range for the PMs). Example: paroxetine.
If you plan a parallel study, phenotyping is almost mandatory. Imagine a situation where you have by chance 5% slow metabolizers in one group, and 10% in the other; you results will be useless (the difference in concentrations will reflect the phenotypes, and not a difference in formulations). In such a case both groups should consist of an equal number of fast/slow metabolizers.