Fluvoxamine
Fluvoxamine. SSRI — also a strong CYP1A2 inhibitor (raises clozapine, theophylline, melatonin, caffeine to clinically meaningful degrees).… Oral half-life 15 h.
SSRI — also a strong CYP1A2 inhibitor (raises clozapine, theophylline, melatonin, caffeine to clinically meaningful degrees). FDA-approved for OCD; off-label for depression + early COVID-19 (the "TOGETHER" trial).
PK: THE BETTER SOURCE WAS ALREADY IN refs[] AND CITED BY NOTHING. van Harten states F verbatim - "Despite complete absorption, oral bioavailability in man is approximately 50% on account of first-pass hepatic metabolism" - where a targeted search for a 53% figure returns zero hits. t-half 16 was a RANGE-INTERIOR value: the previously cited review says "a mean half-life of 15 hours and a range from 9 hours to 28 hours", and two other sources bracket 15 at 12-15 and 15-20. ka 0.4 is removed as unsourced. V 1750 L, about 25 L/kg, appears in NO abstract I could reach - not in the cited review, not in van Harten, not in Perucca - and is retained with that stated, because the resolver default would be worse than a label figure. FLUVOXAMINE IS THE ONE RECORD IN ITS GROUP WITH NO ANALYTE AMBIGUITY AT ALL: it "does not have an asymmetric carbon in its structure and therefore does not exist as optical isomers", and of nine identified metabolites "none of which are known to be pharmacologically active". Its 77% protein binding is confirmed verbatim and is described as "low compared with that of other SSRIs", so class analogies from the other SSRIs do not transfer to it. Its keo note checks out verbatim against the cited PET study. INTERACTIONS: ALL NINE AFFINITIES RECONSTRUCT EXACTLY FROM ONE ASSUMED CONCENTRATION OF 0.16 µM, and two of the notes state it outright. THE BLOCK IS UNUSUALLY WELL BUILT UNDERNEATH THE MISLABELLING: four of the nine were derived from a reported CLEARANCE fall rather than an exposure rise and were correctly inverted as reciprocals, and the ratios span a hundred-fold — from 1.55 for olanzapine to 128 for ramelteon — with the same constant fitting every one. That is a coherent model of one inhibitor, not nine independent guesses. What was wrong is only that a reader of the DATA, as opposed to the prose, saw nine bare affinities against papers that contain none.
Pharmacokinetics
- Oral — t½ 15 h · F 50% · Vd 1750 L
Related compounds
- Caffeine — major
- Theophylline — major
- Melatonin — major
- Olanzapine — warn
- Duloxetine — major
- Ramelteon — contraindicated
- Tizanidine — contraindicated
- Clozapine — caution
Sources: PMID:10668847, PMID:15545309, PMID:18307373, PMID:20478852, PMID:15060511, PMID:9184622