Effects of body weight, smoking status, and sex on plasma concentrations of once-monthly paliperidone palmitate

ABSTRACT

Objectives

Knowledge about the impact of body composition features on pharmacokinetics of newer long-acting injectable antipsychotics is limited.

Methods

We analyzed steady-state plasma concentrations of paliperidone in different body mass index (BMI), age, sex, and smoking status patient subgroups treated with once-monthly paliperidone palmitate (PP1M). Paliperidone plasma concentrations and dose-adjusted-plasma concentrations (C/D) from a therapeutic drug monitoring (TDM) database of PP1M-treated patients were compared among normal BMI, overweight, and obese patients as well as between females vs. males, elderly vs. non-elderly, and smokers vs. non-smokers using non-parametric tests.

Results

In a total of 183 PP1M-treated patients, we found highly variable paliperidone plasma concentrations between individuals but no significant effect of PP1M dose or dosing intervals (p> 0.05). C/D ratios were similar in 54 obese, 82 overweight, and 47 normal BMI patients (p> 0.05). Females had 13.7% higher C/D ratios compared to males, yet this difference was not significant (p> 0.05). No differences were found between elderly vs. non-elderly patients or for smokers vs. non-smokers (p> 0.05).

Conclusion

Our findings suggest that age, sex, smoking, or body weight may not substantially affect pharmacokinetic indices of PP1M. The high interindividual variation of plasma concentrations implies that TDM may be helpful to enhance PP1M efficacy and tolerability.

KEYWORDS:

• Paliperidone palmitate
• paliperidone
• long-acting injectable
• therapeutic drug monitoring (TDM)
• obesity
• smoking

Acknowledgments

The authors express their gratitude to the people who contributed with excellent professional technical and pharmacological competence to the KONBEST database.

Author contributions

G Schoretsanitis, E Haen, A Conca, D Piacentino, M Paulzen, G Grunder, C Hiemke and K Endres participated in research design. G Schoretsanitis and M Paulzen performed data analysis. G Schoretsanitis, E Haen, A Conca, D Piacentino, M Paulzen, G Grunder, C Hiemke and K Endres wrote or contributed to the writing of the manuscript.

Data availability statement

The data are available from the corresponding author upon reasonable request.

Declaration of interest

E Haen received speaker’s or consultancy fees from the following pharmaceutical companies: Servier, Novartis, and Janssen-Cilag. He is managing director of AGATE. He reports no conflict of interest with this publication. C Hiemke has received speaker’s or consultancy fees from Otsuka. He reports no conflict of interest with this publication. A Conca has served as a consultant for Lilly, Bristol-Myers Squibb, and Pfizer. He has served on the speakers’ bureau of Lilly, BMS, Astra Zeneca, Lundbeck, Italfarma, and Janssen. G Gründer has served as a consultant for Allergan, Boehringer Ingelheim, Institute for Quality and Efficiency in Health Care (IQWiG), JanssenCilag, Lundbeck, Otsuka, Recordati, Sage, and Takeda. He has served on the speakers’ bureau of Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Recordati. He has received grant support from Boehringer Ingelheim, Lundbeck, and Saladax. He is co-founder and/or shareholder of Mind and Brain Institute GmbH, OVID Health Systems GmbH and MIND Foundation gGmbH. M Paulzen has received speaker’s fees from Janssen, ROVI, Neuraxpharm, Lundbeck and Otsuka. He has served as a consultant for Novartis. G Schoretsanitis has served as a consultant for HLS Therapeutics. All of the above mentioned authors report no conflict of interest with this publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Ethics approval

This study was approved by the local regulatory authorities of RWTH Aachen University Hospital, Aachen, Germany.

Reviewer disclosures

A reviewer on this manuscript has disclosed receiving speaker fees from Astellas, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Lundbeck, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Nihon Medi-Physics, Novartis, Otsuka Pharmaceutical, Shionogi, Shire, Takeda Pharmaceutical, Tsumura, Wiley Japan, and Yoshitomi Yakuhin, and research grants from Dainippon Sumitomo Pharma, Eisai, Mochida Pharmaceutical, Meiji Seika Pharma and Shionogi. Another reviewer on this manuscript has disclosed being a consultant for, received grants/research support and honoraria from, and been on the speakers/advisory board or has received honoraria from talks and/or consultancy from Adamed, Angelini, Casen-Recordati, Ferrer, Janssen-Cilag, Lundbeck, Neuraxpharm, Otsuka, Pfizer and Sanofi, and grants from the Spanish Ministry of Health, and Instituto de Salud Carlos III (PI20/01066). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.