Olanzapine
Olanzapine. D2 + 5-HT2A antagonist with significant H1, M1, α1 activity → potent but metabolically problematic. Schizophrenia + bipolar I… Oral half-life 33 h.
D2 + 5-HT2A antagonist with significant H1, M1, α1 activity → potent but metabolically problematic. Schizophrenia + bipolar I efficacy among top antipsychotics but weight gain / dyslipidemia are dose-limiting. Olanzapine + samidorphan (Lybalvi) attempts to blunt the weight gain via opioid mechanisms.
PK: THE INTRAMUSCULAR ROW IS A DEPOT AND CARRIED THE ORAL HALF-LIFE. Its own citation says the depot half-life is "~30 days, controlled by the slow rate of intramuscular absorption rather than the 30-h elimination rate-based half-life of oral olanzapine" — so the stored 33 h was about 24-fold wrong and inverted the paper point. It is corrected to 720 h. The oral half-life of 33 h is now cited to Callaghan 1999 (PMID:10511917), verbatim "Its mean half-life in healthy individuals was 33 hours", flagged as a review rather than a primary; the previous citation was a metabolic phenotyping study stating none of the four values. V 1000 L dropped: it is shared verbatim with four unrelated drugs and fails the paper own arithmetic, since a clearance of 26 L/h with a 33 h half-life implies about 1238 L. PK: ABSORPTION RATE AUTHORED FROM OPEN-ACCESS FULL TEXT (PMC4186727). This row carried no ka, so the solver substituted 1.0/h and put the peak at 7.0 h. Verbatim: "After injection of OLAI, the mean observed olanzapine plasma concentration stemming from both formulations reached a peak on day 2 and olanzapine concentrations remained in all patients in the study throughout a period of 4 weeks" — OLAI being the long-acting injection, and the surrounding paragraph establishes that the measurement excludes carry-over from the prior oral dose. THE PRECISION IS COARSE — a peak located to a day, not an hour — and that is recorded rather than smoothed over. NOTE THAT THIS IS THE RECORD OWN CITED SOURCE FOR THIS ROUTE — the number was in the paper already pointed at, in the full text rather than the abstract, so no pass over abstracts could have found it. 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 0.09708/h, which reproduces 48 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC, so only the shape moves. PK: A COHERENT ONE-COMPARTMENT PARAMETER SET WAS SITTING IN THE FULL TEXT OF THE PAPER THIS RECORD CITES FOR ITS OTHER ROUTE. Verbatim: "for oral olanzapine administration, the simulation was based on a 20 mg oral dose for a one-compartment model [absorption rate constant (k a )=0.3/h; elimination rate constant (k el )]=0.0231/h; volume of distribution (V d )=1100 L]", which the authors describe as representing "typical olanzapine pharmacokinetic properties for a daily oral dose (20 mg) with an elimination half-life of 30 h and a clearance of 25 L/h". IT IS A MODELLING PARAMETERISATION RATHER THAN A FITTED MEASUREMENT, AND THAT IS SAID PLAINLY — but it is a ONE-COMPARTMENT set, which is exactly the structure this solver consumes, and it is internally consistent: at the half-life this record already stores it implies 23.1 L/h against the paper stated 25. ONLY THE ORAL HALF IS TAKEN. The same paragraph goes on to change the parameters for the long-acting injection, so the 1,100 L does NOT describe the depot route, whose volume remains an open gap.
Pharmacokinetics
- Oral — t½ 33 h · ka 0.3 h⁻¹ · Vd 1100 L
- Intramuscular — t½ 30.0 d · F 100% · ka 0.09708 h⁻¹
Sources: PMID:10511917, PMID:9659858, PMID:22726212, PMID:12629531, PMID:24815672