Doxepin (antidepressant doses)

pharmacological · nervous · Oral

Doxepin (antidepressant doses). Tertiary-amine TCA — at antidepressant doses (75–300 mg) acts as a non-selective serotonin + NE reuptake… Oral half-life 18 h.

Tertiary-amine TCA — at antidepressant doses (75–300 mg) acts as a non-selective serotonin + NE reuptake inhibitor + H1 antagonist + muscarinic antagonist. Distinct from doxepin-low-dose-for-sleep entry which uses just the H1 effect at 3–6 mg.

PK: ITS CITATION WAS A TWO-FORMULATION BIOEQUIVALENCE STUDY WITH NO INTRAVENOUS ARM, which cannot support a volume, a half-life or an absolute bioavailability, and it reports AUC, Cmax and tmax only. ka 2.0 is that tmax: "Time to reach doxepin maximum plasma concentration (tmax) was 1.98 h for both preparations" - the confirmed hours-as-rate collision, and the only number in the abstract it could have come from. THE STORED F WAS RIGHT AND ITS CITATION WAS WRONG: 0.29 is verbatim in an intravenous-plus-oral crossover, "The mean fraction absorbed after oral administration was 0.29 for each isomer", and independently corroborated by "first-pass metabolism of DOX was 71%". Because the only volume anywhere in this literature is explicitly apparent - "The mean total apparent volume of distribution was 22.7 l/kg" from an oral-only study - F is pinned to 1 and the volume moves to that figure, which corrects a threefold under-prediction of plasma concentration that the previous pairing produced. t-half 15 was stated by nothing and becomes the verbatim 17.9 h. TWO CORRECTIONS TO OUR OWN PROSE: doxepin is NOT a racemate but a mixture of geometric isomers, "Z:E = 15:85", and the claim that desmethyldoxepin free fraction is twice the parent is REFUTED - the two papers give 21.4 versus 20.4 percent unbound and 76.0 versus 75.5 percent bound. Doxepin partitions into erythrocytes with a time-dependent ratio.

Pharmacokinetics

Sources: PMID:6146381, PMID:7113722, PMID:12162857, PMID:7293791