TABLE 3

Fraction unbound of probe substrates and antidiabetic drugs in liver S9 of ZDF and SD rats

Incubation was conducted with 1 μM compound and liver S9 protein concentrations as described in Materials and Methods. Results shown represent mean ± standard deviation of six replicates.

Probe SubstrateTestosteroneMidazolam4-MU7-Hydroxycoumarin
SDZDFSDZDFSDZDFSDZDF
Fraction unbound0.78 ± 0.080.88 ± 0.05a0.82 ± 0.030.89 ± 0.04b0.92 ± 0.030.93 ± 0.021.00c1.00c
DrugRosiglitazoneGlibenclamideCanagliflozinTroglitazone
SDZDFSDZDFSDZDFSDZDF
Fraction unbound0.81 ± 0.010.89 ± 0.040.73 ± 0.010.77 ± 0.050.49 ± 0.030.65 ± 0.05b0.43 ± 0.030.61 ± 0.06b

  • ↵a P < 0.05 in Student’s t test.

  • ↵b P < 0.01.

  • ↵c No detectable binding.