Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia
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Background: Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Methods: Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. Findings: The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441–882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. Conclusions: This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice.
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Aripiprazole lauroxil is supplied as an aqueous suspension for intramuscular injection in either the deltoid (lowest dose only; 441 mg) or gluteal regions (any dose).
“Aripiprazole lauroxil is supplied as an aqueous suspension for intramuscular injection in either the deltoid (lowest dose only; 441 mg) or gluteal regions (any dose) [63].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [63]
The introductory passage following the Abstract’s Conclusions describes an aqueous suspension injected into the gluteal or deltoid muscle. The paper discusses 441-, 662-, and 882-mg doses, but the passages do not establish that only 441 mg may be injected in the deltoid or that every dose may be injected in the gluteal muscle. Page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOnce injected, aripiprazole lauroxil slowly dissolves into the systemic circulation, where it is first converted to N-hydroxymethyl aripiprazole and lauric acid; the N-hydroxymethyl group is subsequently removed by rapid hydrolysis, releasing active aripiprazole.
“Once injected, aripiprazole lauroxil slowly dissolves into the systemic circulation, where it is first converted to N-hydroxymethyl aripiprazole and lauric acid; the N-hydroxymethyl group is subsequently removed by rapid hydrolysis, releasing active aripiprazole [63].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [63]
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Experimental — accuracy not yet measuredPeak plasma concentrations of aripiprazole lauroxil are attained approximately 41 days after a single administration.
“Peak plasma concentrations are attained approximately 41 days after a single administration [63].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [63]
The Results (Population Pharmacokinetics of Aripiprazole Lauroxil) state that maximal plasma concentrations are attained approximately 41 days after a single aripiprazole lauroxil administration. The measured substance is aripiprazole, however, not aripiprazole lauroxil as the claim specifies. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAripiprazole lauroxil is administered every 4 weeks (441 mg, 662 mg, or 882 mg), every 6 weeks (882 mg), or every 8 weeks (1064 mg).
“Aripiprazole lauroxil is administered every 4 weeks (441 mg, 662 mg, or 882 mg), every 6 weeks (882 mg), or every 8 weeks (1064 mg).”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [63]
The Results (Simulations; page unavailable) describe 441 mg, 662 mg, and 882 mg every 4 weeks and model 882 mg every 6 weeks. The paper does not address the claimed 1064 mg every 8 weeks; its discussion of an 8-week gap concerns resuming treatment after a missed dose, not a scheduled regimen. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAripiprazole lauroxil consists of the nonester prodrug N-lauroyloxymethyl aripiprazole.
“Aripiprazole lauroxil, another long-acting formulation of aripiprazole, consists of the nonester prodrug N-lauroyloxymethyl aripiprazole [63].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [63]
When aripiprazole lauroxil was first approved, oral supplementation with aripiprazole was recommended for 21 days following initiation.
“When aripiprazole lauroxil was first approved, oral supplementation with aripiprazole was recommended for 21 days following initiation [63, 68].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [63]
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“Thus, consideration of factors beyond the elimination phase is important to understand the complex nature of LAI drug-release profiles and to optimize clinical effectiveness.(18) Our results suggest the potential use of PopPK modeling to identify an additional dose (662 mg q4wk) and dose interval (882 mg q6wk) not stu…”
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Self-citation
- Authors
- Hard, M. L., Mills, R. J., Sadler, B. M., Turncliff, R. Z., & Citrome, L.
- Affiliations
- New York Medical College (US)
- Corresponding author
- Hard, Marjie L.
- Turncliff, Ryan Z.
- ORCID
- Citrome, Leslie
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2017-06
- Volume
- 37
- Issue
- 3
- Pages
- 289-295
- ISSN
- 0271-0749 (ISSN-L)
- 1533-712X
- PMC
- PMC5400404
- OpenAlex
- W2599566543
- Cited by
- 51
- References
- 21
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 9 · 2022: 6 · 2021: 11 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 6
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Touro Scholar (Touro College) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- aripiprazole lauroxil, intramuscular injection, schizophrenia, population pharmacokinetic model, long-acting antipsychotics, drug release kinetics
- MeSH terms
- Aripiprazole, Clinical Trials as Topic, Delayed-Action Preparations, Humans, Injections, Intramuscular, Models, Theoretical, Schizophrenia, Antipsychotic Agents
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