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).