Table 2. PK Properties of TRH and TRH Mimetics 64, 68–70 in Rat Plasmaa.
| compounds | CL (mL/min/kg) | t1/2 (min)b | Vdss (L/kg) | MRT (min)c | BA (%)d | fu (%)e |
|---|---|---|---|---|---|---|
| TRH | 89.2 | 3.0 | 0.33 | 3.7 | NCf | NCf |
| 64 | 13.0 | 13.5 | 0.19 | 14.3 | 1.1 | >99 |
| 68 | 14.2 | 9.8 | 0.16 | 11.0 | NCf | >99 |
| 69 | 17.4 | 26.2 | 0.25 | 14.6 | NCf | >99 |
| 70 | 30.6 | 21.6 | 0.58 | 19.1 | 4.7 | >99 |
a
Each value represents the mean of two animals.
b
t1/2 of the plasma concentration (Cp,iv) of TRH mimetic after intravenous administration to rats were calculated by interpolation for plasma concentration of terminal phase.
c
MRT for the plasma concentration (Cp,iv) of TRH mimetic after intravenous administration to rats was calculated as defined in eq 1 by numerical integration using a linear trapezoidal formula and extrapolation to infinite time based on a monoexponential equation.54
d
BA
values of TRH mimetic after oral
administration were calculated as defined in eq 2 using the plasma concentration after intravenous (Cp,iv) and oral administrations (Cp,po).
 |
 |
e
fu: free fraction ratio in serum (%).
f
NC: not calculated.