TABLE 3

Pharmacokinetic parameters of MDZ and 1′-OH MDZ following intrahepatic portal vein administration of MDZ (0.15 mg/kg/h for 4 h) to monkeys dosed with vehicle or compound A (6 mg/kg i.v.)

Values are mean ± S.D., n = 4. Values in parentheses are range.


Compound Measured

Parameters

Vehicle Control

Compound A (6 mg/kg i.v.)
% of control
MDZ AUC0-last (μM · h) 0.037 ± 0.02 0.304 ± 0.17* 1062 ± 753 (483-2072)
AUC0-inf (μM · h) 0.040 ± 0.02 0.328 ± 0.21* 1022 ± 695 (478-1943)
t1/2 (h) 0.9 ± 0.4 1.0 ± 0.5 119 ± 20 (95-136)
1′-OH MDZ AUC0-inf (μM · h) 0.063 ± 0.04 0.170 ± 0.09* 439 ± 350 (101-889)
1′-OH MDZ/MDZ Ratio AUC0-inf 1.6 ± 0.7 0.55 ± 0.07* 39 ± 12 (21-46)
Compound A AUC0-last (μM · h) 6.73 ± 1.61

Cmax (μM)

1.88 ± 0.35

  • * Statistically significant difference from control (P < 0.05).