Georgios Schoretsanitis1,2, Ekkehard Haen3,4, Daria Piacentino5,6, Andreas Conca5, Katharina Endres3,4, Fabio Carpi5, Christoph Hiemke7, Gerhard Gründer8, Michael Paulzen9,10,11. 1. The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Behavioral Health Pavilion, 7559 263rd Street, Glen Oaks, NY, 11004, USA. george.schor@gmail.com. 2. University Hospital of Psychiatry Zurich, Zurich, Switzerland. george.schor@gmail.com. 3. Clinical Pharmacology, Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany. 4. Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany. 5. Psychiatric Service of the Health District of Bolzano, Bolzano, Italy. 6. Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, The National Institutes of Health, Bethesda, MD, USA. 7. Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz, Germany. 8. Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. 9. Alexianer Hospital Aachen, Aachen, Germany. 10. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany. 11. JARA-Translational Brain Medicine, Aachen, Germany.
Abstract
OBJECTIVE: The objective of this study was to investigate associations between pharmacokinetic correlates and once-monthly paliperidone palmitate (PP1M)-related adverse drug reactions (ADRs). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVE: The objective of this study was to investigate associations between pharmacokinetic correlates and once-monthly paliperidone palmitate (PP1M)-related adverse drug reactions (ADRs). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Georgios Schoretsanitis; Edoardo Spina; Christoph Hiemke; Jose de Leon Journal: Expert Rev Clin Pharmacol Date: 2017-07-12 Impact factor: 5.045
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