Flumazenil
Flumazenil. Competitive GABA-A benzodiazepine-site antagonist — reverses benzodiazepine sedation in overdose / procedural over-sedation. Short… IV half-life 1.2 h.
Competitive GABA-A benzodiazepine-site antagonist — reverses benzodiazepine sedation in overdose / procedural over-sedation. Short half-life requires re-dosing after long-acting BZD overdose. Precipitates seizures in chronic BZD users + mixed-overdose with TCAs.
PK: BOTH STORED NUMBERS CAME FROM RANGES, AND ONLY ONE OF THEM MATTERED. The volume was the midpoint of "apparent distribution volume 0.6-1 kg" (sic, L/kg) and the half-life was the LOW ENDPOINT of "the short half-life of 0.7-1.3 h" — but the PAIRING SURVIVED ITS ARITHMETIC WITH ROOM, implying 55.5 L/h against that same review "high plasma and blood clearance of 520-1300 ml min-1" and within 3% of a verbatim 53.8. RECORDED SO NOBODY REWRITES A PASSING CLEARANCE. The half-life is the defect, and IT ERRED IN THE DANGEROUS DIRECTION: 0.7 h UNDERSTATES RE-SEDATION, which is this drug entire clinical hazard. Both replacements are verbatim in one twelve-volunteer study — "total body clearance, 53.8 +/- 1.2 L/h ... and elimination half-life, 70.2 +/- 9.9 min" — and the volume is that clearance over that rate, so the passing clearance is preserved exactly while the duration lengthens 1.67-fold. A DEEPER LIMIT IS RECORDED, NOT PAPERED OVER: the same abstract gives "initial volume of distribution, 16 +/- 5.7L ... distribution half-life, 4.1 +/- 1.3 min", so the model initial concentration is roughly a third of the true one — AND FOR A REVERSAL AGENT WITH A ONE-TO-TWO-MINUTE ONSET THE DISTRIBUTION PHASE IS THE DRUG. On the antagonism question: the occupancy row models flumazenil alone with no benzodiazepine term, which is INCOMPLETE RATHER THAN WRONG, since what matters clinically is the fraction of the site flumazenil holds.
Pharmacokinetics
- IV — t½ 1.2 h · F 100% · Vd 90.8 L
Sources: PMID:2842128, PMID:6268754, PMID:3127102, PMID:2044332