Fluoxetine
Fluoxetine. Selective serotonin reuptake inhibitor — blocks SERT. Active metabolite norfluoxetine has 7–15 day t½, buffering missed doses +… Oral half-life 2.2 d.
Selective serotonin reuptake inhibitor — blocks SERT. Active metabolite norfluoxetine has 7–15 day t½, buffering missed doses + causing prolonged withdrawal. Weak 5-HT2C antagonism contributes to activation / norepinephrine release. CYP2D6 inhibitor (strong) — interaction-rich.
PK: t½ 48 h IS TWO DAYS, THE MIDPOINT OF ITS CITED "half-life of 1-3 days". A stated mean exists instead — "The mean t1/2 was 6.6 vs. 2.2 days ... for patients with cirrhosis vs. normal volunteers" — and 2.2 days is now carried. THE WRONG-ANALYTE CHECK IS CLEAN: the stored value is the parent, not norfluoxetine 7-15 days. But a single-dose half-life materially under-represents chronic dosing, because this drug inhibits its own clearance — "approximately 2 days (6 days after multiple doses)" — and the schema cannot express that. V 700 L is refuted by arithmetic: it implies a clearance of 3.4 mL/min/kg against a verbatim 9.6, so the record runs 2.8 TIMES TOO SLOW and over-predicts exposure by the same factor. No abstract states a fluoxetine volume in litres at all, so nothing is substituted. F 0.7 IS UNSOURCEABLE IN PRINCIPLE — fluoxetine has never had an intravenous formulation, so no absolute bioavailability has ever been measured. Both are retained only because the resolver defaults would be worse. ka 0.4 is unsourced. INTERACTIONS: THE TWO AFFINITIES IMPLY ASSUMED CONCENTRATIONS OF 1.0 AND 7.7 µM, a sevenfold disagreement within one block, so neither can be relabelled on the evidence available. Left undeclared rather than forced into agreement. PK: ABSORPTION RATE AUTHORED FROM THE PROZAC LABEL. This row carried no ka, so the solver substituted 1.0/h and put the peak at 4.4 h. Source, verbatim from the current FDA label (DailyMed setid c88f33ed-6dfb-4c5e-bc01-d8e36dd97299): "In man, following a single oral 40 mg dose, peak plasma concentrations of fluoxetine from 15 to 55 ng/mL are observed after 6 to 8 hours." RANGE: the shorter endpoint is taken. PUBMED HAS THIS NOWHERE — 27 targeted searches across two passes returned four usable peak times for this whole class, because Tmax is a label figure that rarely reaches an abstract. A regulatory label is already a first-class source in this schema. With the stored half-life fixing ke, Tmax solves uniquely for ka by inverting the model own definition, ln(ka/ke)/(ka-ke) = Tmax — ARITHMETIC, NOT AN ESTIMATE — giving 0.6681/h, which reproduces 6 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC, so only the shape moves.
Pharmacokinetics
- Oral — t½ 2.2 d · F 70% · ka 0.6681 h⁻¹ · Vd 700 L
Related compounds
- St. John's Wort — contraindicated
- Desipramine — major
- Risperidone — warn
Sources: PMID:10674711, PMID:8195463, PMID:11985287, PMID:15121647, PMID:3262026