Pharmacokinetic (PK) parameters of MDZ and 1′-OH MDZ following intrahepatic portal vein administration of MDZ (0.5 mg/kg/h for 4 h) to rhesus monkeys pretreated with vehicle (PEG 400) or rifampin (1.8 or 18 mg/kg p.o.) for 5 days
Values are mean ± S.D., n = 4. Values in parentheses are range.
Compound Measured | PK Parameters | Vehicle Control | Rifampin | ||||||
|---|---|---|---|---|---|---|---|---|---|
| 18 mg/kg | 1.8 mg/kg | ||||||||
| % of control | % of control | ||||||||
| MDZ | AUC0-last (μM · h) | 0.66 ± 0.60 | 0.037 ± 0.03* | 10 ± 4 (6-16) | 0.059 ± 0.04* | 11 ± 3 (7-15) | |||
| AUC0-inf (μM · h) | 0.70 ± 0.66 | 0.045 ± 0.04* | 9 ± 7 (4-17) | 0.072 ± 0.05* | 12 ± 3 (8-16) | ||||
| F h | 0.16 ± 0.13 | 0.010 ± 0.01* | 8 ± 7 (2-19) | N.A. | |||||
| t1/2 (h) | 0.8 ± 0.2 | 1.0 ± 0.5 | 132 ± 59 (74-213) | ||||||
| 1′-OH MDZ | AUC0-inf (μM · h) | 0.923 ± 0.38 | 0.071 ± 0.06* | 9 ± 7 (3-15) | 0.133 ± 0.08* | 15 ± 6 (7-20) | |||
| 1′-OH MDZ/MDZ Ratio | AUC0-inf (μM · h) | 2.0 ± 1.4 | 3.0 ± 2.6 | 143 ± 117 (51-312) | 2.5 ± 1.8 | 120 ± 41 (72-172) | |||
| Rifampin | AUC0-last (μM · h) | 67.37 ± 24.41 | 1.24 ± 1.17 | ||||||
|
| Cmax (μM) |
| 14.80 ± 4.94 |
| 0.32 ± 0.26 |
| |||
N.A., not available.
↵* Statistically significant difference from control (P < 0.05).