Pharmacokinetic profile after multiple deltoid or gluteal intramuscular injections of paliperidone palmitate in patients with schizophrenia
Abstract
Paliperidone palmitate (PP) is a once‐monthly long‐acting injectable antipsychotic approved for the treatment of schizophrenia in many countries. To evaluate the different injection‐site options, we compared the pharmacokinetic profile of paliperidone after multiple injections of PP 100 mg eq. (156 mg of PP, equivalent to 100 mg of paliperidone) on days 1, 8, 36, and 64 into the deltoid (n = 24) or gluteal muscle (n = 25) in patients with schizophrenia. After four injections in the deltoid muscle, paliperidone exposure was higher for AUC τ and C max, compared with the gluteal muscle (geometric mean AUC τ‐based ratio: 120% [90% CI: 93.1–154.7%], and geometric mean C max‐based ratio: 130% [90% CI: 100.6–168.9%]). The mean [SD] fluctuation index was higher, with a larger interpatient variability, after deltoid‐injections (75.9% [30.9%]) than gluteal‐injections (58.5% [14.3%]). The median t max was similar for both sites. PP was generally tolerable in patients, with more favorable local‐site tolerability for gluteal‐injection. In conclusion, to achieve therapeutic‐concentrations quickly, the first‐two injections of PP are best administered into the deltoid muscle, whereas thereafter maintenance‐injections can be administered either in the deltoid or gluteal muscle.
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Paliperidone palmitate is the long-acting esterified formulation of paliperidone that is available in formulations for administration once monthly (PP1M) and once every 3 months (PP3M).
“Paliperidone palmitate is the long-acting esterified formulation of paliperidone that is available in formulations for administration once monthly (PP1M) and once every 3 months (PP3M) [74, 75].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [75]
The recommended PP1M initiation dosing regimen consists of an injection of 234 mg on day 1 and 156 mg on day 8 ± 4 days; both doses are administered in the deltoid muscle because of its higher vascularity than the gluteal muscle.
“The recommended PP1M initiation dosing regimen consists of an injection of 234 mg on day 1 and 156 mg on day 8 ± 4 days; both doses are administered in the deltoid muscle because of its higher vascularity than the gluteal muscle [75, 77].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [75]
The recommended initial monthly maintenance dose of PP1M is 117 mg (injected into the deltoid or gluteal regions), although some patients can benefit from maintenance dose adjustments ranging from 39 to 234 mg, with an allowable window of ±7 days.
“The recommended initial monthly maintenance dose is 117 mg (injected into the deltoid or gluteal regions), although some patients can benefit from maintenance dose adjustments ranging from 39 to 234 mg, with an allowable window of ±7 days to provide scheduling flexibility [75, 77].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [75]
Doses of the paliperidone palmitate formulations reflect the amount of covalently bonded molecule.
“Similar to aripiprazole lauroxil, doses of the paliperidone palmitate formulations reflect the amount of covalently bonded molecule.”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [75]
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“injection-sites, which was in agreement with the results from other studies.(16,27) For the gluteal muscle, the increase in the mean predose plasma concentration of paliperidone after day 8 suggested that steady-state was not completely achieved after two injections of PP in the gluteal muscle.”
ResultSelf-citationCleton, A., Rossenu, S., Crauwels, H., Berwaerts, J., Hough, D., Gopal, S., Eerdekens, M., Vandebosch, A., Remmerie, B., De Meulder, M., et al. (2014) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.295 · Cited by 48 · see citing works
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Self-citation
- Authors
- Rossenu, S., Cleton, A., Hough, D., Crauwels, H., Vandebosch, A., Berwaerts, J., Eerdekens, M., Herben, V., De Meulder, M., Remmerie, B., & Francetic, I.
- Affiliations
- Janssen (Belgium) (BE)
- Janssen Research & Development (United States) (US)
- Division of Janssen Pharmaceutica NV Janssen Research & Development Beerse Belgium
- Institute of Clinical Pharmacology Clinical Hospital Centre Zagreb Croatia
- Corresponding author
- Remmerie, Bart
- Venue
- Clinical Pharmacology in Drug Development
- Publisher
- Wiley
- Published
- 2014-08-28
- Volume
- 4
- Issue
- 4
- Pages
- 270-278
- ISSN
- 2160-763X (ISSN-L)
- 2160-7648
- OpenAlex
- W1953171524
- Cited by
- 26
- References
- 27
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 2
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology in Drug Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- paliperidone palmitate, long-acting injectable antipsychotics, schizophrenia, injection site comparison, pharmacokinetics, fluctuation index, interpatient variability, local tolerance
- MeSH terms
- Paliperidone Palmitate, Adolescent, Adult, Aged, Buttocks, Female, Humans, Injections, Intramuscular, Male, Metabolic Clearance Rate, Middle Aged, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Treatment Outcome, Drug Monitoring, Croatia, Area Under Curve, Young Adult, Deltoid Muscle
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