TABLE 6

Effects of miR-34a on in vitro intrinsic clearance of P450 probe substrates

Values represent means ± S.D. (n = 5 per group).

SubstrateTreatmentt1/2CLint
minml/min per mg protein
MDZControl2.52 ± 0.260.20 ± 0.04
miR-34a2.60 ± 0.340.24 ± 0.08
PHEControl14.62 ± 6.270.09 ± 0.02
miR-34a12.56 ± 2.190.11 ± 0.01
DXMControl14.34 ± 2.550.10 ± 0.01
miR-34a18.49 ± 1.38*0.07 ± 0.01*
  • DXM intrinsic clearance was marginally attenuated in liver microsomes derived from mice treated with miR-34a agent, compared with the control. Data were fit to a monoexponential decay model (or biphasic decay for MDZ) to derive t1/2 and CLint. DIC and CLZ data are not fit to any model because there was minimal substrate depletion.

  • ** P < 0.01.