TABLE 3

Liver and systemic exposure of E7766 in wild-type and humanized mice in the presence or the absence of Rifampicin

ParametersWT Mice 0.5 mg/kg E7766WT Mice 0.5 mg/kg E7766 +RifampicinHu Mice 1.0 mg/kg E7766Hu Mice 0.5 mg/kg E7766 +Rifampicin
AUCtotal (ng∙h/ml)56.0300126 ± 48.7302 ± 92.2
AUCtotal/dose (ng∙h/ml/[mg/kg])112600126 ± 48.7604 ± 184
CLtot,p (l/h per kilogram)8.931.729.20 ± 4.651.80 ± 0.619
Vss (l/kg)1.660.5205.93 ± 5.961.29 ± 0.243
Liver AUCtotal (ng·h/g)44604250
Liver Kp,total79.614.2
  • AUCtotal/dose, area under the total plasma conc.-time curve normalized by dose; Hu, OATP1B1/OATP1B3-humanized mouse; liver AUCtotal, area under the total liver conc.-time curve. Values represent the mean ± S.D. (n = 3).