Pharmacokinetics of olanzapine long-acting injection: the clinical perspective
Open accessAbstract
Olanzapine long-acting injection (OLAI) is a sustained-release depot antipsychotic for the treatment of schizophrenia in adults. Our objective was to explain the pharmacokinetics of OLAI to provide clinical insight. Simulation models and data from clinical trials are presented. Olanzapine concentrations were observed immediately upon injection. Half-life was ∼30 days, controlled by the slow rate of intramuscular absorption rather than the 30-h elimination rate-based half-life of oral olanzapine. As each injection builds on the drug still being released from previous injections, concentrations increase gradually until a steady state is reached after ∼3 months. Concentrations were similar to oral olanzapine and proportional to the dose; the average steady-state concentrations (10th-90th percentile) for the 150, 210, and 300 mg/2-week doses were 16-32, 15-55, and 20-67 ng/ml, respectively, and those for the 300 and 405 mg/4-week doses were 19-48 and 19-62 ng/ml, respectively. Peak concentrations most often occurred at 2-4 days after injection. Peak-to-trough fluctuation was greater for the 4-week dosing interval than the 2-week one, with no apparent clinical ramifications for these differences. Trough concentrations were above the lower end of the therapeutic range, even at the first injection. Long-term use up to 6 years indicated no additional accumulation. The impact of smoking and sex was similar, but less pronounced than for oral olanzapine.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In cases of rapid olanzapine pamoate dissolution, patients may experience signs and symptoms consistent with olanzapine overdose, known as post-injection delirium/sedation syndrome (PDSS); the risk of PDSS, noted in a boxed warning, requires monitoring for at least 3 h after each injection.
“In these cases, patients may experience signs and symptoms consistent with olanzapine overdose, known as post-injection delirium/sedation syndrome (PDSS); the risk of PDSS, noted in a boxed warning in the prescribing information, requires monitoring for at least 3 h after each injection [70, 72].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [70]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredOlanzapine pamoate is a long-acting formulation of olanzapine, comprising a low-solubility salt of pamoic acid and olanzapine, suspended in an aqueous solution for intramuscular gluteal injection.
“Olanzapine pamoate is a long-acting formulation of olanzapine, comprising a low-solubility salt of pamoic acid and olanzapine, suspended in an aqueous solution for intramuscular gluteal injection [70, 71].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [70]
The Introduction identifies olanzapine pamoate as a long-acting intramuscular depot salt that dissolves slowly after injection into the gluteal muscle. The Results and clinical considerations section describes it as a suspension of a poorly soluble salt. Neither passage specifies that the suspension is aqueous. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPeak plasma concentrations of olanzapine pamoate appear after 2-6 days, and the apparent half-life is 30 days.
“Peak plasma concentrations appear after 2–6 days [70, 71], and the apparent half-life is 30 days [70].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [70]
If the olanzapine pamoate salt comes into contact with the blood, possibly from a nicked blood vessel during administration, the salt rapidly dissolves within minutes to hours after injection, resulting in supratherapeutic concentrations.
“If the salt comes into contact with the blood, possibly from a nicked blood vessel during administration, the salt rapidly dissolves within minutes to hours after injection of the drug, resulting in supratherapeutic concentrations [70].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [70]
After intramuscular injection, the olanzapine pamoate salt slowly dissolves in intramuscular fluid into olanzapine (free base), pamoic acid, and other acids and bases.
“After intramuscular injection, the salt slowly dissolves in intramuscular fluid into olanzapine (free base), pamoic acid, and other acids and bases.”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [70]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011
Hiemke, C., Baumann, P., Bergemann, N., Conca, A., Dietmaier, O., Egberts, K. M., Fric, M., Gerlach, M., Greiner, C., Gründer, G., et al. (2011) · Pharmacopsychiatry · doi:10.1055/s-0031-1286287 · Cited by 862 · see citing works
Tiihonen, J., Haukka, J., Taylor, M., Haddad, P. M., Patel, M. X., & Korhonen, P. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10081224 · Cited by 619 · see citing works
Robinson, D. G., Woerner, M. G., McMeniman, M., Mendelowitz, A., & Bilder, R. M. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.3.473 · Cited by 590 · see citing works
Callaghan, J. T., Bergstrom, R. F., Ptak, L. R., & Beasley, C. M. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199937030-00001 · Cited by 544 · see citing works
Self-citationLeucht, C., Heres, S., Kane, J. M., Kissling, W., Davis, J. M., & Leucht, S. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2010.11.020 · Cited by 419 · see citing works
Self-citationWagner, J. G., & Nelson, E. (1964) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600531126 · Cited by 410 · see citing works
Fulton, B., & Goa, K. L. (1997) · Drugs · doi:10.2165/00003495-199753020-00007 · Cited by 251 · see citing works
Kane, J. M., Detke, H. C., Naber, D., Sethuraman, G., Lin, D., Bergstrom, R. F., & McDonnell, D. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.07081221 · Cited by 196 · see citing works
Self-citationDetke, H. C., Zhao, F., Garhyan, P., Carlson, J., & McDonnell, D. (2011) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e32834093d1 · Cited by 185 · cited 2× · see citing works
“These loading-dose recommendations are principally based on theoretical considerations on the risk of relapse (Detke et al., 2011).”
BackgroundSelf-citationCarrillo, J. A., Herráiz, A. G., Ramos, S., Gervasini, G., Vizcaíno, S., & Benítez, J. (2003) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200304000-00003 · Cited by 177 · see citing works
Gex‐Fabry, M., Balant-Gorgia, A. E., & Balant, L. P. (2003) · Therapeutic Drug Monitoring · doi:10.1097/00007691-200302000-00007 · Cited by 167 · see citing works
Detke, H. C., McDonnell, D., Brunner, E., Zhao, F., Sorsaburu, S., Stefaniak, V. J., & Corya, S. A. (2010) · BMC Psychiatry · doi:10.1186/1471-244x-10-43 · Cited by 118 · see citing works
Self-citationIntramuscular Preparations of Antipsychotics
Altamura, A. C., Sassella, F., Santini, A., Montresor, C., Fumagalli, S., & Mundo, E. (2003) · Drugs · doi:10.2165/00003495-200363050-00004 · Cited by 116 · see citing works
Psychopharmacology: Atypical Antipsychotic Dosing: The Effect of Smoking and Caffeine
de León, J. (2004) · Psychiatric Services · doi:10.1176/appi.ps.55.5.491 · Cited by 115 · see citing works
Therapeutic Drug Monitoring of Common Antipsychotics
Patteet, L., Morrens, M., Maudens, K. E. K., Niemegeers, P., Sabbe, B., & Neels, H. M. (2012) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e3182708ec5 · Cited by 106 · see citing works
Catlow, J. T., Barton, R. D., Clements, M., Gillespie, T. A., Goodwin, M., & Swanson, S. P. (1995) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/0378-4347(95)00061-m · Cited by 106 · see citing works
McDonnell, D. P., Detke, H. C., Bergstrom, R. F., Kothare, P., Johnson, J., Stickelmeyer, M., Sanchez-Felix, M. V., Sorsaburu, S., & Mitchell, M. I. (2010) · BMC Psychiatry · doi:10.1186/1471-244x-10-45 · Cited by 96 · see citing works
Self-citationUchida, H., Takeuchi, H., Graff-Guerrero, A., Suzuki, T., Watanabe, K., & Mamo, D. C. (2011) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318218d339 · Cited by 94 · see citing works
Equivalent Switching Dose From Oral Risperidone to Risperidone Long-Acting Injection
Bai, Y. M., Chen, T. T., Chen, J. Y., Wu, W.-H., Hung, C. H., & Lin, W. K. (2007) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v68n0808 · Cited by 91 · see citing works
Long-acting injectable antipsychotics: focus on olanzapine pamoate
Lindenmayer, J. (2010) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s3072 · Cited by 68 · see citing works
Skogh, E., Sjödin, I., Josefsson, M., & Dahl, M. (2010) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318204d9e2 · Cited by 55 · see citing works
Olanzapine Long-Acting Injection
Frampton, J. E. (2010) · Drugs · doi:10.2165/11204930-000000000-00000 · Cited by 40 · see citing works
Ballenger, J. C. (2012) · Yearbook of Psychiatry and Applied Mental Health · doi:10.1016/j.ypsy.2011.10.012 · Cited by 40 · see citing works
McDonnell, D., Kryzhanovskaya, L. A., Zhao, F., Detke, H. C., & Feldman, P. D. (2011) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1225 · Cited by 35 · see citing works
Self-citationPharmacokinetic studies of antipsychotics in healthy volunteers versus patients.
Cutler, N. R. (2001) · PubMed · Cited by 32 · see citing works
Are there clinically useful predictors and early warning signs for pending relapse?
Gäebel, W., & Riesbeck, M. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.08.003 · Cited by 32 · see citing works
Mitchell, M., Kothare, P., Bergstrom, R., Zhao, F., Jen, K. Y., Walker, D., Johnson, J., & McDonnell, D. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.09.023 · Cited by 31 · see citing works
Self-citationUse of risperidone long-acting injectable in a rural border community clinic in southern california.
Camacho, A., Ng, B., Galangue, B., & Feifel, D. (2008) · PubMed Central · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Bergstrom RF Callaghan JT Cerimele BJ Kurtz DI Hatcher BL Tran PV Bymaster FP Tye N Herrera J Breier A Tollefson GD Population pharmacokinetics and plasma concentrations of olanzapine. Olanzapine (Zyprexa): a novel antipsychotic 2000 Philadelphia, PA: Lippincott Williams and Wilkins; 232– 252
Cited by
Sorted by citations
Correll, C. U., Kim, E., Sliwa, J. K., Hamm, W., Gopal, S., Mathews, M., Venkatasubramanian, R., & Saklad, S. R. (2021) · CNS Drugs · doi:10.1007/s40263-020-00779-5 · Cited by 205 · see citing works
Hard, M. L., Mills, R. J., Sadler, B. M., Turncliff, R. Z., & Citrome, L. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000691 · Cited by 51 · see citing works
- Authors
- Heres, S., Kraemer, S., Bergstrom, R. F., & Detke, H. C.
- Affiliations
- Butler University (US)
- Eli Lilly (Germany) (DE)
- Eli Lilly (United States) (US)
- Corresponding author
- Heres, Stephan
- Venue
- International Clinical Psychopharmacology
- Published
- 2014-11
- Volume
- 29
- Issue
- 6
- Pages
- 299-312
- ISSN
- 0268-1315 (ISSN-L)
- PMC
- PMC4186727
- OpenAlex
- W1973930084
- Cited by
- 50
- References
- 28
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 2
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- International Clinical Psychopharmacology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc-nd)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- pharmacokinetics, long-acting injectable antipsychotics, schizophrenia, steady-state drug concentration, dosing interval, drug accumulation, health effects of smoking, sex differences, computer simulation
- MeSH terms
- Olanzapine, Administration, Oral, Adolescent, Adult, Aged, Benzodiazepines, Clinical Trials as Topic, Computer Simulation, Delayed-Action Preparations, Female, Humans, Injections, Intramuscular, Male, Middle Aged, Models, Biological, Sex Characteristics, Smoking, Time Factors, Antipsychotic Agents, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
