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Review
. 2021 Jan;35(1):39-59.
doi: 10.1007/s40263-020-00779-5. Epub 2021 Jan 28.

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview

Christoph U Correll  1   2   3 , Edward Kim  4 , Jennifer Kern Sliwa  4 , Wayne Hamm  5 , Srihari Gopal  6 , Maju Mathews  6 , Raja Venkatasubramanian  6 , Stephen R Saklad  7   8
Affiliations
Review

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview

Christoph U Correll et al. CNS Drugs. 2021 Jan.

Erratum in

Abstract

The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics. A systematic search of the PubMed database was conducted to identify physical and formulation properties and pharmacokinetic data of commercially available LAI antipsychotics, including flupentixol decanoate, fluphenazine decanoate, haloperidol decanoate, zuclopenthixol decanoate, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate, risperidone microspheres, and risperidone polymeric microspheres. Additional information was obtained from package inserts and product monographs. Relevant data on drug properties, administration details, pharmacokinetic parameters, and oral dose equivalencies of LAI antipsychotics are summarized. Based on our analysis, formulation characteristics (e.g., vehicle medium) and administration characteristics (e.g., injection site) can affect rate of absorption and adverse effects and may factor into whether oral supplementation or an additional injection is needed. Dose adjustments may be necessary based on potential drug-drug interactions, and approximate dose equivalence with oral formulations can help inform titration when switching from oral to LAI formulations. Clinicians administering LAI antipsychotics should consider these formulation and pharmacokinetic factors to maximize clinical impact and to adjust to an individual patient's needs and treatment goals.

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Conflict of interest statement

SRS is an employee of The University of Texas at Austin, College of Pharmacy, Pharmacotherapy Division. He was appointed to the Texas Health and Human Services Commission, San Antonio State Hospital and the UT Health San Antonio, Long School of Medicine; has been a consultant for Alkermes, Intra-Cellular Therapies, Genomind, Karuna, and Otsuka; has participated in speakers bureaux for Alkermes, Intra-Cellular Therapies, Neurocrine, and Teva; has served as speaker for several professional organizations; has been on the Business Development Council for the College of Psychiatric and Neurologic Pharmacists; was the Treasurer (term ended 2019) for the College of Psychiatric and Neurologic Pharmacists Foundation; and has served as an expert witness on both defendant and plaintiff sides. He has no direct stock ownership in pharmaceutical corporations. CUC has been a consultant and/or advisor to or has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He has provided expert testimony for Janssen and Otsuka; served on a data safety monitoring board for Lundbeck, Rovi, Supernus, and Teva; received grant support from the Berlin Institute of Health, Janssen, the National Institute of Mental Health, the Patient-Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation; and received royalties from UpToDate. He is also a stock option holder of LB Pharma. JKS, SG, MM, WH, and RV are employees and shareholders of Johnson & Johnson. EK is a former employee and shareholder of Johnson & Johnson.

Figures

Fig. 1
Fig. 1
Flip-flop pharmacokinetics. A Equation used to calculate concentration at time t. B Representative concentration–time curves. Cmax maximum concentration, Cp plasma concentration at time t, F bioavailability, kfast absorption rate constant for an oral drug and elimination rate constant for an LAI, kslow absorption rate constant for an LAI and elimination rate constant for an oral drug, LAI long-acting injectable, t time, tmax time to maximum concentration, Vd volume of distribution
Fig. 2
Fig. 2
Peak-to-trough plasma concentration ratios of oral and long-acting injectable antipsychotics at steady state [, –121]. AL aripiprazole lauroxil, AM aripiprazole monohydrate, ER extended release, LAI long-acting injectable, PP1M paliperidone palmitate once monthly, PP3M paliperidone palmitate every 3 months, qxw every x weeks, RLAI-MS risperidone long-acting injection microspheres
Fig. 3
Fig. 3
PRISMA flow diagram. LAI long-acting injectable, PK pharmacokinetics, PI package insert
See this image and copyright information in PMC

References

    1. Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1:15067. - PubMed
    1. Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry. 2018;17(2):149–60. - PMC - PubMed
    1. Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, et al. Practice guideline for the treatment of patients with schizophrenia. 2nd ed. Washington: American Psychiatric Association; 2010. - PubMed
    1. Kaplan G, Casoy J, Zummo J. Impact of long-acting injectable antipsychotics on medication adherence and clinical, functional, and economic outcomes of schizophrenia. Patient Prefer Adherence. 2013;7:1171–80. - PMC - PubMed
    1. Weiden PJ. Redefining medication adherence in the treatment of schizophrenia: how current approaches to adherence lead to misinformation and threaten therapeutic relationships. Psychiatr Clin N Am. 2016;39(2):199–216. - PubMed

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