Table 1.
Pharmacokinetic parameters of midazolam and α‐hydroxy‐midazolam in healthy subjects after administration of a single dose of 2.5 mg midazolam intravenous (IV) or 2.5 or 5 mg midazolam intranasal (IN)
| Treatment | AUC 0–∞ (ng h ml −1 ) | C max ( ng ml −1 ) | t 1/2 (h) | T max (min) | F | |
|---|---|---|---|---|---|---|
| Midazolam | Midazolam 2.5 mg IV | 93.9 (33.8) | 219.2 (68.1) | 3.6 (29.4) | 2.0 (1.2–3.0) | 1 |
| Midazolam 2.5 mg IN | 65.6 (49.0)** | 30.6 (42.3) | 6.3 (123.4)* | 10.9 (6.0–24.0) | 0.74 (0.28–1.85) | |
| Midazolam 5 mg IN | 131.9 (26.0) | 66.2 (31.5) | 4.3 (31.0) | 13.8 (9.0–24.0) | 0.76 (0.45–1.20) | |
| α‐hydroxy‐midazolam | Midazolam 2.5 mg IV | 15.83 (36.9) | 6.1 (37.2) | 4.6 (45.5) | 14.4 (9.0–21.0) | |
| Midazolam 2.5 mg IN | 10.9 (54.1) | 2.4 (55.5) | 5.3 (40.0) | 45.4 (24.0–240.0) | ||
| Midazolam 5 mg IN | 24.0 (37.5) | 5.3 (34.5) | 6.3 (44.2) | 50.6 (21.0–121.2) |
For one (*) or two (**) subjects, adjusted r‐squared was <0.800 and/or %AUC extrapolated to infinity was >20%. When parameters were excluded, AUC0‐infinity was 56.5 (37.9) ng h ml−1 and t1/2 was 4.4 (24) hours.
AUC, C max and half‐lives are expressed as geometric mean (CV%); T max and F are expressed as geometric mean (range); AUC, area under the curve; C max, peak plasma concentration; CV, coefficient of variation; F, bioavailability; IV, intravenous; IN, intranasal; t1/2, elimination half‐life; Tmax, time to reach Cmax