Quetiapine
Quetiapine. Multi-receptor antagonist with strong H1 + α1 activity → sedation. Brief D2 occupancy ('fast dissociation') → low EPS. Active… Oral half-life 7 h.
Multi-receptor antagonist with strong H1 + α1 activity → sedation. Brief D2 occupancy ('fast dissociation') → low EPS. Active metabolite norquetiapine adds NET inhibition + 5-HT1A partial agonism (rationale for MDD adjunct indication).
PK: REFUTED BY ITS OWN CITATION, TWICE, AND BOTH FIXES ARE FREE. The stored t-half of 6 h becomes 7: the cited abstract says "The drug is eliminated with a mean terminal half-life of approximately 7 hours", and an independent patient study agrees at "approximately 7 h for quetiapine". F 0.9 is refuted by the same abstract in the opposite direction - "The absolute bioavailability is unknown, but the RELATIVE bioavailability from orally administered tablets compared with a solution was nearly complete" - which is the confirmed relative-read-as-absolute shape; F is pinned to 1 because V 700 L is the label 10 L/kg apparent figure. ka 2.02 is a member of the 1.5-hour generator: with the old half-life it solves to Tmax 1.503 h, the exact midpoint of the abstract "ranging from 1 to 2 hours", while the measured immediate-release Tmax is 2 h. I did NOT swap in the one published apparent volume, 277 L, because it comes from an extended-release study and pairs with a 2.2 h half-life that contradicts everything else. The formulation question is settled and is NOT a half-life problem: "modifying the formulation does not change the overall absorption or elimination of quetiapine". My earlier 83%-bound finding is re-confirmed here verbatim.
Pharmacokinetics
- Oral — t½ 7 h · F 100% · Vd 700 L
Sources: PMID:11510628, PMID:38282365, PMID:9430133, PMID:12176106, PMID:8935801, PMID:26436896