Cariprazine
Cariprazine. D3-preferring D3/D2 partial agonist with high D3 affinity (in vivo brain D3 occupancy at therapeutic doses — unusual among… Oral half-life 3 d.
D3-preferring D3/D2 partial agonist with high D3 affinity (in vivo brain D3 occupancy at therapeutic doses — unusual among antipsychotics). Also 5-HT1A partial agonism and 5-HT2B antagonism. Two active metabolites: desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR); DDCAR has a multi-week terminal half-life, giving cariprazine uniquely long effective duration after discontinuation.
PK: A HUMAN PET MEASUREMENT PINS THIS RECORD ERROR, AND THE MISSING VOLUME — NOT THE AFFINITY — WAS THE CAUSE. With no volume stored, the solver silently substituted 0.5 L/kg, putting steady-state cariprazine at 185 ng/mL on 3 mg daily and driving modelled D2 occupancy to 98.7% — AGAINST ITS OWN CITATION VERBATIM "Doses >= 1.5 mg/d yielded 69 - 75% D2/D3 receptor occupancy as measured in positron emission tomography scans". Back-solving from that anchor gives about a thousand litres, i.e. THE CONCENTRATION SCALE WAS ROUGHLY THIRTYFOLD TOO HIGH. The value stored is that PET-anchored figure and is disclosed as derived: no cariprazine volume appears in ANY indexed abstract — the population analysis, the paediatric studies, the interaction study and the orodispersible bioequivalence study all report structure or ratios only. MY WRONG-MASS PRIOR IS REFUTED: the stored mass IS the free base, the species the PK claims to describe, and both occupancy conversions check exactly. THE REAL OCCUPANCY DEFECT IS DIFFERENT AND IS LOGGED: the two rows come from mutually inconsistent scales, encoding a 63-fold selectivity where this record own other reference says about tenfold — and the PET anchor ACQUITS THE D2 ROW, since the stored affinity requires a steady-state concentration in exactly the real therapeutic range while the alternative would require one far below it. THE HALF-LIFE IS ALSO THE WRONG ANALYTE: "Terminal half-lives of cariprazine, desmethyl-cariprazine, and didesmethyl-cariprazine ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446 hours", so the stored 72 h sits ABOVE the parent own measured range while the total active moiety runs about a week. PK: THE ABSENT ABSORPTION RATE IS ACQUITTED AGAINST OPEN-ACCESS FULL TEXT. With no ka the solver substitutes 1.0/h and renders a peak at 4.7 h, and PMC13269304 states "Cariprazine is rapidly and well absorbed following oral administration, reaching peak plasma concentrations (C max ) approximately 3 to 6 h post-dose" — SO THE DEFAULT FALLS INSIDE THE PUBLISHED RANGE. Nothing is authored: storing a number would assert a measurement where the honest description is that the default happens to land correctly. A SEPARATE CAVEAT IS LEFT STANDING: this record models the parent, whose active metabolite DDCAR has a far longer half-life and accumulates over weeks, so the single-dose shape corrected here is not the whole pharmacology.
Pharmacokinetics
- Oral — t½ 3.0 d · F 50% · Vd 1000 L
Sources: PMID:23320989, PMID:22537450, PMID:20093397, PMID:26834462, PMID:23966785, PMID:41689599