First, based on previous findings of
increased parent pioglitazone concentrations in the presence
of gemfibrozil, we only measured parent pioglitazone
concentrations in our study [5, 18]. Pioglitazone is
metabolized to a number of different active metabolites,
namely M-III, and M-IV [4]. A previous study found no significant
differences in M-III or M-IV plasma exposure
between CYP2C8 genotype groups [31]. However,
M-III : parent and M-IV : parent AUC ratios were significantly
greater in carriers of CYP2C8 *3 allele compared
with wild-type homozygotes