Table 1.
The pharmacokinetic variables of midazolam and 1′-hydroxymidazolam and the pharmacodynamic variables in nine healthy subjects after 7.5 mg oral midazolam, following intake of a combined OC preparation or placebo once daily for 10 days.
| Variable | OC phase | Placebo phase (control) | Mean percentage difference between OC and placebo (95% CI) |
|---|---|---|---|
| Midazolam | |||
| AUC (ng ml−1 h) | 72 ± 16* | 60 ± 13 | 21% (2% to 40%) |
| Cmax (ng ml−1) | 36 ± 8.6 | 31 ± 9.3 | 24% (−12% to 61%) |
| tmax (h) | 1 (0.5−1.5) | 1 (0.5−1) | – |
| t½ (h) | 2.1 ± 0.9 | 1.9 ± 0.7 | 22% (−20% to 64%) |
| 1′-Hydroxymidazolam | |||
| AUC (ng ml−1 h) | 21 ± 2.5* | 30 ± 8.1 | −25% (−10% to −41%) |
| Cmax (ng ml−1) | 12 ± 2.1 | 15 ± 5.1 | −13% (−35% to 9%) |
| tmax (h) | 1 (0.5−1.5) | 1 (0.5−1) | – |
| t½ (h) | 1.0 ± 0.2 | 1.3 ± 0.3 | −21% (−42% to 1%) |
| Metabolic ratio | 0.31 ± 0.08* | 0.54 ± 0.23 | −36% (−19% to −53%) |
| Pharmacodynamic variables† | |||
| Subjective drowsiness (VAS) (mm h) | 291 ± 38.1 | 284 ± 68.7 | 10% (−18% to 37%) |
| DSST (digits h) | 886 ± 89.7 | 870 ± 119 | 3% (−3% to 8%) |
| Button clicks (clicks h) | 1160 ± 79.5 | 1160 ± 71.3 | 0% (−2% to 2%) |
Data are mean ± s.d.; tmax values are given as median with range.
*
Significantly (P < 0.05) different from the placebo phase.
†
Shown as areas under the effect against time curve from 0 to 8 h [AUC(0,8 h)] calculated by the linear trapezoidal rule.