Use of pharmacogenetics in bioequivalence studies to reduce sample size: an example with mirtazapine and CYP2D6

Abstract

In bioequivalence studies, intra-individual variability (CV_w) is critical in determining sample size. In particular, highly variable drugs may require enrolment of a greater number of subjects. We hypothesize that a strategy to reduce pharmacokinetic CV_w, and hence sample size and costs, would be to include subjects with decreased metabolic enzyme capacity for the drug under study. Therefore, two mirtazapine studies, two-way, two-period crossover design (n=68) were re-analysed to calculate the total CV_w and the CV_ws in three different CYP2D6 genotype groups (0, 1 and ⩾2 active genes). The results showed that a 29.2 or 15.3% sample size reduction would have been possible if the recruitment had been of individuals carrying just 0 or 0 plus 1 CYP2D6 active genes, due to the lower CV_w. This suggests that there may be a role for pharmacogenetics in the design of bioequivalence studies to reduce sample size and costs, thus introducing a new paradigm for the biopharmaceutical evaluation of drug products.