TABLE 2

Unbound fraction of TREO and S,S-EBDM in rat plasma and brain homogenate

MatrixAnalyteConcentrationaUnbound fractionb
PlasmaTREO2.3 μM0.962 ± 0.137
57 μM0.940 ± 0.061
2000 μM0.960 ± 0.163
S,S-EBDM3.5 μM1.083 ± 0.211
87 μM0.986 ± 0.119
Brain homogenateTREO2.3 μM1.063 ± 0.172
5.7 μM0.999 ± 0.081
17.2 μM1.000 ± 0.108
S,S-EBDM3.5 μM1.092 ± 0.079
8.7 μM0.974 ± 0.075
  • a The used concentrations covered the range observed in the JR and the YAR that received TREO 500 mg/kg b.wt. as an intravenous bolus.

  • b At each concentration level of TREO or S,S-EBDM the unbound fraction was determined using five lots of plasma and brain homogenate obtained from different 2-mo-old rat donors.