Aripiprazole
Aripiprazole. D2 + 5-HT1A partial agonist + 5-HT2A antagonist. Partial agonism acts as 'dopaminergic stabiliser' — reduces DA tone in mesolimbic… Oral half-life 3.1 d.
D2 + 5-HT1A partial agonist + 5-HT2A antagonist. Partial agonism acts as 'dopaminergic stabiliser' — reduces DA tone in mesolimbic hyperactivity, elevates it in mesocortical hypoactivity. Lower EPS + prolactin elevation than typical antipsychotics; metabolic side effects still present but less than olanzapine/quetiapine.
PK: ITS INTRAMUSCULAR ROUTE WAS A DEPOT BOLTED ONTO IMMEDIATE-RELEASE DOSES. PMID:28350572 is ARIPIPRAZOLE LAUROXIL, a monthly extended-release prodrug dosed at "441-882 mg dosed monthly", and its 36-day release window (zo_dur 864 h, which is verbatim) sat beside a 10-30 mg dose block that belongs to the immediate-release agitation injection studied in a different paper. As stored the solver delivered about 16.7 mg over 36 days where the real depot delivers 441-882 mg, a THIRTY- TO FIFTY-FOLD under-delivery, and it applied the ORAL terminal half-life to a depot with flip-flop kinetics. lag_hr 130 was interpolated from "after 5 to 6 days" (120-144 h). The route is removed rather than patched; aripiprazole lauroxil is a different product and deserves its own record. F 0.87 is real but was hung on a paper that says 0.85 verbatim - "the geometric mean values for the absolute bioavailability of aripiprazole following oral and intramuscular administration were 0.85 and 0.98" - so the record now stores what its own citation states. V 343 L is the label 4.9 L/kg, which is an IV steady-state figure, so CLASS 6 IS ACQUITTED and pairing it with an independent F is correct. ka 1.4 is a DISCLOSED Tmax inversion reproducing Kubo 3.6 h, not a measurement, and now says so. ITS keo IS THE COUNTER-EXAMPLE TO MY OWN STANDING CLAIM: Kim 2012 fits a real effect compartment, keo 0.725 with a 12.9% RSE, and it is left untouched. PK ANALYTE: DECLARED PARENT, because this record cited study measures two molecules and the record stores one of them. Verbatim, that paper determined "The noncompartmental pharmacokinetic parameters for plasma concentrations of aripiprazole and its active metabolite dehydro-aripiprazole", and the bioavailability stored here is unambiguously the parent figure — "the geometric mean values for the absolute bioavailability of aripiprazole following oral and intramuscular administration were 0.85 and 0.98". WHAT THIS DOES NOT FIX, AND SHOULD BE SAID: the active metabolite carries a substantial share of exposure at steady state and has its own longer half-life, so a parent-only curve understates the active material at the receptor. The occupancy rows on this record are therefore driven by the smaller half of the pharmacology. Logged rather than modelled, since authoring a metabolite chain needs a formation fraction this abstract does not state.
Pharmacokinetics
- Oral — t½ 3.1 d · F 85% · Vd 343 L
Sources: PMID:18563956, PMID:22186667, PMID:17242925, PMID:17965519, PMID:15257633, PMID:12065741