Clonazepam
Clonazepam. Benzodiazepine — GABA-A positive allosteric modulator. Long t½ makes it better for generalised anxiety / seizure prophylaxis… Oral half-life 39 h.
Benzodiazepine — GABA-A positive allosteric modulator. Long t½ makes it better for generalised anxiety / seizure prophylaxis; dependence profile still significant.
PK: THE BEST-SOURCED RECORD OF ITS GROUP, and three of four values verify against a three-way intravenous, intramuscular and oral crossover — so every parameter has an intravenous anchor. Each was also the RIGHT selection from among several in the same sentence: F 0.9 is the oral 90% and not the intramuscular 93% nor an average; the half-life is "p.o. 39.0 h" and not the intravenous 38.0 nor the mean of three; and V 180 L is a terminal volume from a study containing a real intravenous arm, so class 6 does not apply. ka 2.5 is a back-derivation to a suspiciously round 1.99 h rather than to that paper own verbatim oral time to peak of 1.7 h. THE MODEL-CLASS ERROR I EXPECTED IS ABSENT: its effect-compartment value is not fitted to a seizure-frequency endpoint over weeks — it is unsourced clinical folklore, honestly flagged, which is a lesser and different problem. The genuine benzodiazepine EEG effect-compartment models were chased and rejected: one publishes no rate at all and finds ACUTE TOLERANCE, which would make a naive value wrong anyway; the other is a different drug, given intravenously, in sheep.
Pharmacokinetics
- Oral — t½ 39 h · F 90% · Vd 180 L
Sources: PMID:2872063, PMID:3424402