Impact of age and gender on paliperidone exposure in patients after administration of long-acting injectable formulations—an observational study using blood samples from 1223 patients

Abstract

Purpose

Paliperidone palmitate is an antipsychotic medication available as long-acting injectable (LAI) formulations. The aim of this study was to investigate the effect of age and gender on paliperidone exposure after administration of LAI formulations.

Methods

Data on serum concentrations of paliperidone from patients using LAI during were included retrospectively from a therapeutic drug monitoring (TDM) service. Information about dose was obtained from the requisition forms. As a measure of exposure, daily dose-adjusted serum concentration (C/D ratio) was used. Based on initial analysis of C/D ratios versus age, a breaking point close to 50 years was observed, thus deciding the grouping of patients as older (≥50 years) or younger (15–49 years). Linear mixed model analyses, allowing multiple measurements per patients, were used.

Results

In total, 1223 patients were included, whereof 1158 patients used paliperidone LAI in once-monthly intervals. In these patients (27.9% older), older patients had significantly higher paliperidone C/D ratio than younger patients (+20%, p<0.001). Compared to males, females had higher C/D ratio (+14%; p<0.001). Subsequently, older female users of once-monthly LAI intervals had 41% higher paliperidone C/D ratios compared to younger males (15.0 vs. 21.2 nM/mg; p<0.001). Compared to females aged 21–30 years, females with high age (≥70 years) had at least 105% higher paliperidone C/D ratio (p<0.001).

Conclusion

The present study shows that older age and female gender are associated with higher paliperidone exposure than younger age and males, respectively. Particularly, older female patients (>50 years) are likely exposed to high concentration and cautious dosing in this subgroup is required.

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Fig. 1

Data Availability

The data that supports the findings of this study are available upon reasonable request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions.

Code availability

Not applicable.

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Funding

This work was funded by the South-Eastern Norway Regional Health Authority (grant number 2017085).

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Authors

Contributions

All authors were involved in the ideation, conceptualizing and design of the study. RLS and MT collected and prepared the data material. RLS analysed the data. RLS, MT and GH interpreted the data. MT, RLS and GH drafted the manuscript. All other authors critically reviewed the manuscript and approved the submitted version.

Corresponding author

Correspondence to Marit Tveito.

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Ethics approval

The study was approved by the Regional Committee for Medical and Health Research Ethics (2017/9121) and Health Research Ethics and the Hospital Investigational Review Board.

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The use of historical patient data for the purpose of this study was approved by the Regional Committee for Medical and Health Research Ethics and the Hospital Investigational Review Board without consent from the patients, as the study was based on retrospective data only.

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All authors have approved the submission.

Conflict of interest

Prof. Molden has received speaker´s honoraria from Lundbeck and Lilly. The other authors have no conflicts of interest to declare.

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Tveito, M., Høiseth, G., Haslemo, T. et al. Impact of age and gender on paliperidone exposure in patients after administration of long-acting injectable formulations—an observational study using blood samples from 1223 patients. Eur J Clin Pharmacol (2021). https://doi.org/10.1007/s00228-021-03114-z

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Keywords

  • Paliperidone
  • Antipsychotics
  • Long-acting injectable
  • Age
  • Females