Table 2.
Benzodiazepine pharmacokinetic and pharmacodynamic characteristics by route of administration [14,18,19,20,22,23,24,25,26,28,29,30,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46].
| Agent | Dose (maximum) |
Route | Onset (min) |
Duration of Action | Bioavailability (%) |
Volume of Distribution (L/kg) |
Metabolism | Excretion | T1/2
(h) |
|---|---|---|---|---|---|---|---|---|---|
| Lorazepam (Ativan® Injection) |
0.1 mg/kg (4 mg) |
IV | 1.6 | 4–6 h | 100 | 1.3 | Liver to inactive metabolites | Hepatic metabolism to inactive metabolites | 12 |
| - | IM | 12–19 | 83–100 | ||||||
| Lorazepam (Ativan Intensol®) |
0.1 mg/kg (4 mg) |
SL | Readily | - | 90 | ||||
| Lorazepam (Ativan® Sublingual tablets) * |
0.1 mg/kg (4 mg) |
SL | 15–17 | - | >90 | ||||
| Midazolam (Versed®) |
0.2 mg/kg (10 mg) |
IV | 1.5–2.5 | 30–80 min | 100 | 1–3 | CYP3A4 to active metabolite | Renal | 3–4 |
| Midazolam (Versed®) |
0.2 mg/kg (10 mg) |
IM | 5–15 | 2–6 h | >90 | 3–5 | |||
| Midazolam (Nayzilam®) |
0.2 mg/kg (15 mg) |
IN | 3–10 | 23 min | 44 | 2–6 | |||
| Midazolam | 0.2 mg/kg (15 mg) |
IV injection given IN | 6–14 | - | 44–83 | 2–4 | |||
| Midazolam (Buccolam®, Epistatus®) * |
0.5 mg/kg (30 mg) |
Buccal | 5–15 | - | 75–87 | 3–4 | |||
| Midazolam (Versed®) |
0.5 mg/kg (30 mg) |
IV injection given Buccal | ~15 | - | 75 | - | |||
| Diazepam (Valium®) |
0.15 mg/kg (10 mg) |
IV | 1–3 | 15–30 min | 100 | 0.8–1.2 | CYP2C19 and CYP3A4 to active metabolites | Renal | 33–45 |
| Diazepam (Valium®) |
- | IM | ~15 | - | >90 | 60–72 | |||
| Diazepam (Valtoco®) |
0.2 mg/kg (20 mg) |
IN | 2–10 | 15–30 min | 97 | ~49 | |||
| Diazepam | 0.2 mg/kg (20 mg) |
IV injection given IN | 1–10 | - | Up to 74 | 17–33 | |||
| Diazepam (Diastat®) |
0.2 mg/kg (20 mg) |
PR | 2–10 | 15–30 min | 90 | ~46 | |||
| Clobazam (Onfi®) |
0.2 mg/kg (40 mg) |
Oral Susp |
19–30 | - | 87 | 100 | CYP2C19 and CYP3A4 to active metabolites | Renal | 16–82 |
| Clobazam (Sympazan®) |
0.2 mg/kg (40 mg) |
Oral Film |
* Not available in the US; IV injectable solution is used for buccal administration in the US; IM, intramuscular; IN, intranasal; IV, intravenous; PR, rectal; Susp, suspension. Ativan® sublingual tablet manufactured by Pfizer Inc., Kirkland, Quebec, Canada. Buccolam® Shire Pharmaceuticals Ireland Limited, Dublin, Ireland. Veriton Pharma, Weybridge, Surrey, UK.