Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation
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ORIGINAL RESEARCH ARTICLE
Elevated Clozapine Concentrations in Clozapine‑Treated Patients with Hypersalivation Georgios Schoretsanitis1 · Maxim Kuzin2 · John M. Kane1,3,4 · Christoph Hiemke5 · Michael Paulzen6,7,8 · Ekkehard Haen9,10 Accepted: 11 September 2020 © Springer Nature Switzerland AG 2020
Abstract Background and Objective Hypersalivation is a common, clozapine-related adverse drug reaction with a serious impact on quality of life. Pharmacokinetic correlates of clozapine-related hypersalivation have evaded attention. The purpose of this study was to compare pharmacokinetic parameters between clozapine-treated patients with vs. without hypersalivation from a large therapeutic drug monitoring database. Methods Out of a large therapeutic drug monitoring dataset of clozapine-treated patients, we compared a group of patients with hypersalivation (n = 72) and a control group of patients without any adverse reactions in this regard (n = 323). Comparisons included plasma concentrations and concentrations-by-dose as well as demographic characteristics between groups. Post-hoc analyses were performed separately in smokers and non-smokers. We used the non-parametric Mann–Whitney U test and the chi-square test, while effects of confounders were assessed using a bootstrapping analysis of covariance. Results Patients with hypersalivation had higher clozapine plasma concentrations and concentrations-by-dose (p
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