The Pharmacokinetics of Long-Acting Antipsychotic Medications
Abstract
The depot antipsychotics are synthesized by esterification of the active drug to a long chain fatty acid and the resultant compound is then dissolved in a vegetable oil, with the exception of some molecules of new generation characterized by microcrystalline technologies. The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate. The pharmacokinetics of depot antipsychotic medications are such that an intramuscular injection given at intervals from 1 to 4 weeks will produce adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot formulations of antipsychotic drugs have been extensively studied. The clinical pharmacokinetics of the depot antipsychotics for which plasma level studies are available (i.e. fluphenazine enanthate and decanoate, haloperidol decanoate, bromperidol decanoate, clopenthixol decanoate, flupenthixol decanoate, perphenazine onanthat, pipotiazine undecylenate, pipotiazine palmitate, fluspirilene, long-acting injectable risperidone, olanzapine pamoate, paliperidone palmitate, long-acting iloperidone, long-acting injectable aripiprazole) are reviewed. The proper study of these agents has been handicapped until recently by the necessity of accurately measuring subnanomolar concentrations in plasma. Their kinetic properties, the relationship of plasma concentrations to clinical effects, and conversion from oral to injectable therapy are discussed.
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LAI antipsychotics are injected intramuscularly or subcutaneously, and the drug is slowly absorbed from the injection site into the circulation.
“LAI antipsychotics are injected intramuscularly or subcutaneously, and the drug is slowly absorbed from the injection site into the circulation [33].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [33]
The absorption rate of LAI antipsychotics is slower than the elimination rate, resulting in 'flip-flop' kinetics, whereby the time to steady state is a function of absorption, and the concentration at steady state is a function of elimination.
“Therefore, the absorption rate of LAI antipsychotics is slower than the elimination rate, resulting in “flip-flop” kinetics, whereby the time to steady state is a function of absorption, and the concentration at steady state is a function of elimination (Fig. 1) [32, 33].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [33]
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- Authors
- Spanarello, S., & Ferla, T.
- Venue
- Current Clinical Pharmacology
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2014-08-31
- Volume
- 9
- Issue
- 3
- Pages
- 310-317
- ISSN
- 1574-8847 (ISSN-L)
- OpenAlex
- W2005217683
- Cited by
- 70
- References
- 0
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 1 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 6 · 2019: 2 · 2018: 7 · 2017: 9 · 2016: 6 · 2015: 4 · 2014: 1 · 2013: 1
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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
- long-acting injectable antipsychotics, pharmacokinetics, flip-flop kinetics, fluphenazine enanthate, haloperidol decanoate, flupenthixol decanoate, fluspirilene, long-acting injectable risperidone, olanzapine pamoate, paliperidone palmitate, intramuscular injection, relapse prevention, plasma concentration
- MeSH terms
- Animals, Chemistry, Pharmaceutical, Delayed-Action Preparations, Humans, Injections, Intramuscular, Time Factors, Antipsychotic Agents, Medication Adherence
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