What this study adds:
- The low tissue affinity and the inhibitory effect of the parent drug
on M1 canalicular efflux resulted in the high plasma exposure of M1 in
patients
- When co-administrated, the formation of M1 was inhibited by gefitinib,
which was firstly demonstrated to a strong inhibitor of CYP1A1.
- Consideration for metabolite kinetics in DDI studies appears to be
helpful in elucidating the DDI mechanism.