Pharmacokinetic (PK) parameters of MDZ and its metabolites following intravenous administration of MDZ (0.5 mg/kg/h for 4 h) to rhesus monkeys pretreated with vehicle (PEG 400) or rifampin (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) | ||
|---|---|---|---|---|---|
| % of control | |||||
| Plasma | |||||
| MDZ | AUC0-last (μM · h) | 3.79 ± 0.39 | 4.10 ± 0.78 | 109 ± 13 | |
| (97-123) | |||||
| CL (ml/min/kg) | 26.6 ± 3.4 | 25.2 ± 5.6 | 94 ± 13 | ||
| (80-104) | |||||
| Vdss (l/kg) | 1.77 ± 0.50 | 1.70 ± 0.69 | 93 ± 18 | ||
| (67-107) | |||||
| t1/2 (h) | 0.9 ± 0.2 | 0.8 ± 0.3 | 90 ± 28 | ||
| (65-130) | |||||
| 1′-OH MDZ | AUC0-last (μM · h) | 0.52 ± 0.32 | 0.055 ± 0.025* | 13 ± 7 | |
| (6-23) | |||||
| 1′-OH MDZ/MDZ Ratio | AUC0-last | 0.13 ± 0.07 | 0.013 ± 0.004* | 12 ± 6 | |
| (5-18) | |||||
| Urine | |||||
| MDZ | Recovery (% of dose) | 0.03 ± 0.01 | |||
| 1′-OH MDZ | Recovery (% of dose) | 1.6 ± 1.3 | |||
| 1′-OH MDZ glucuronide | Recovery (% of dose) | 64.8 ± 9.0 | |||
| 4-OH MDZ (unconjugate + conjugate) | Recovery (% of dose) | 0.3 ± 0.1 |
|
| |
↵* Statistically significant difference from control (P < 0.05).