The objective of this study was to investigate associations between pharmacokinetic correlates and once-monthly paliperidone palmitate (PP1M)-related adverse drug reactions (ADRs).
Plasma concentrations and dose-adjusted plasma concentrations (‘concentration-by-dose’ [C/D]) of paliperidone from a naturalistic therapeutic drug monitoring database of PP1M-treated patients were compared between patients with ADRs, classified according to the Udvalg for Kliniske Undersogelser side-effect rating scales categories, and patients without ADRs. Analyses included non-parametric tests and a logistic regression model with a significance level set at 0.05.
In 172 patients, we found no differences in sex, age, smoking, body mass index, PP1M dose, paliperidone plasma concentrations, and C/D values (p > 0.05) between 44 patients with and 128 patients without PP1M-related ADRs. We did not detect differences when specifying for different types of ADRs (p > 0.05). Injection intervals were shorter in patients with vs patients without ADRs (p = 0.03). The logistic regression did not report effects for sex, plasma concentrations, or C/D values (p > 0.05). Post hoc analyses in male patients receiving PP1M every 28 weeks reported higher paliperidone concentrations and C/D values in patients with vs without ADRs (p = 0.049 and p = 0.022). Within the group of male patients, we found an odds ratio of 3.07 for PP1M-associated ADRs in patients with C/D values above 7.7 (ng/mL)/(mg/day).
Our findings did not reveal distinct patterns of paliperidone concentrations in patients with PP1M-related ADRs. However, male patients receiving PP1M every 28 days with C/D values higher than 7.7 (ng/mL)/(mg/day) showed a higher risk for ADRs, implying that therapeutic drug monitoring may be useful in assessing the risk of PP1M-related ADRs.
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The authors express their gratitude to the number of people who contributed with excellent professional, technical, as well as pharmacological competence to build up the KONBEST database.
This research did not receive any funding.
Conflicts of interest/Competing interest
Ekkehard Haen received speaker’s or consultancy fees from the following pharmaceutical companies: Servier, Novartis, and Janssen-Cilag. He is the managing director of AGATE. He reports no conflict of interest with this publication. Christoph Hiemke has received speaker’s or consultancy fees from Otsuka. He reports no conflict of interest with this publication. Andreas 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. Gerhard Gründer has served as a consultant for Allergan, Boehringer Ingelheim, Institute for Quality and Efficiency in Health Care, JanssenCilag, Lundbeck, Otsuka, Recordati, Sage, and Takeda. He has served on the speakers’ bureau of Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, and Recordati. He has received grant support from Boehringer Ingelheim, Lundbeck, and Saladax. He is a co-founder and/or shareholder of Mind and Brain Institute GmbH, Brainfoods GmbH, InMediCon GmbH, OVID Health Systems GmbH, and MIND Foundation gGmbH. Michael Paulzen has received speaker’s fees from Neuraxpharm, Lundbeck, and Otsuka. He has served as a consultant for Novartis. He reports no conflict of interest with this publication. Georgios Schoretsanitis, Daria Piacentino, Katharina Endres, and Fabio Carpi have no conflicts of interest that are directly relevant to the content of this article.
This study was approved by the local regulatory authorities of RWTH Aachen University Hospital, Aachen, Germany.
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The data are available from the corresponding author upon reasonable request.
Participated in research design: GS, EH, AC, DP, MP, GG, CH, KE, FC. Performed data analysis: GS, MP. Wrote or contributed to the writing of the manuscript: GS, EH, AC, DP, MP, GG, CH, KE, FC.
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Schoretsanitis, G., Haen, E., Piacentino, D. et al. Pharmacokinetic Correlates of Once-Monthly Paliperidone Palmitate-Related Adverse Drug Reactions. Clin Pharmacokinet (2021). https://doi.org/10.1007/s40262-021-01044-8