Paroxetine
Paroxetine. Most potent SSRI at SERT + has weak anticholinergic + NE reuptake activity. Strong CYP2D6 inhibitor. Shortest t½ among SSRIs → most… Oral half-life 20 h.
Most potent SSRI at SERT + has weak anticholinergic + NE reuptake activity. Strong CYP2D6 inhibitor. Shortest t½ among SSRIs → most notorious discontinuation syndrome.
PK: t-half 20 IS VERIFIED and survives the non-linearity objection. Its citation states "t(1/2) 20.03-/+5.33 h" verbatim, and the steady-state literature agrees - "between 21 (paroxetine) and 36 (citalopram) hr". Autoinhibition of CYP2D6 bites on CLEARANCE and BIOAVAILABILITY, not on the terminal slope: "with repeated administration, bioavailability of paroxetine increases and pharmacokinetics may become nonlinear in some patients", and apparent oral clearance falls markedly on multiple dosing. So F 0.5 is a modelling approximation BY CONSTRUCTION rather than a measurement - paroxetine has no intravenous form and no absolute bioavailability has ever been published - and V 900 is likewise absent from the citation. Both are declared rather than deleted. ka 0.4 is removed for two independent reasons: it is byte-identical to this record own keo_per_h of 0.4, the one-number-two-fields shape, and it implies a peak at 6.7 h against the cited paper own measured "T(max)5.64-/+1.84 h". All eleven references were checked against the three purposes and every one earns its place; the live source_pmid was missing from refs and is added. INTERACTIONS: ALL SEVEN AFFINITIES ARE CALIBRATIONS THROUGH ONE ASSUMED 0.2 µM, and two of the notes already print the arithmetic ("Ki ≈ 0.2/1.38"). THE ASSUMED CONCENTRATION IS NEARLY FOUR TIMES THIS RECORD OWN MODELLED MEAN PLASMA LEVEL, so the model under-produces these interactions at typical dosing — worth stating, because paroxetine is a mechanism-based inhibitor whose real-world effect is if anything larger than a static calculation suggests. Every edge is marked mechanism-based already, which is consistent with the clinical fold-changes and inconsistent with treating the number as a reversible affinity; declaring the basis is what makes that tension visible rather than hidden.
Pharmacokinetics
- Oral — t½ 20 h · F 50% · Vd 900 L
Related compounds
- Tamoxifen — major
- Metoprolol — major
- Atomoxetine — warn
- Desipramine — major
- Risperidone — warn
- Aripiprazole — warn
- Tramadol — warn
- Carvedilol — caution
Sources: PMID:10674711, PMID:10741632, PMID:33245517, PMID:8513845, PMID:11360029, PMID:21739267