Midazolam
Midazolam. Short-acting benzodiazepine — GABA-A α1/α2/α3/α5 positive allosteric modulator. Procedural sedation, anxiolysis, anterograde amnesia.… Oral half-life 2.3 h.
Short-acting benzodiazepine — GABA-A α1/α2/α3/α5 positive allosteric modulator. Procedural sedation, anxiolysis, anterograde amnesia. CYP3A4 substrate — major DDI source (azoles, macrolides, ritonavir massively prolong sedation). Reversible with flumazenil.
PK: Heizmann 1983 (PMID:6138080), 6 volunteers, verbatim "elimination half-life, 2.3 h" and "apparent volume of distribution at steady-state (VSS), 50.2" — the record had the two routes half-lives BACKWARDS, storing 2.5 h on the intravenous row. THE ORAL VOLUME OF 114 L WAS A BACK-CALCULATION: 50.2 divided by 0.44, its own intravenous volume divided by its own bioavailability. Storing both then divided the dose by F twice and understated oral exposure by exactly 1/F, about 2.3-fold. The absolute volume is now carried on both routes so the bioavailability applies once. The intranasal bioavailability of 0.75 is verbatim but specific to a concentrated formulation; a conventional spray measures 50% with an absorption rate of 2.46 /h and a half-life of 3.1 h in one study, which is not blended here. ka values dropped throughout as unstated.
Pharmacokinetics
- IV — t½ 2.3 h · F 100% · Vd 50.2 L
- Oral — t½ 2.3 h · F 44% · Vd 50.2 L
- Intranasal — t½ 2.3 h · F 75%
Sources: PMID:6138080, PMID:27780297, PMID:6638545