Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation

被引:31
作者
Schoretsanitis, Georgios [1 ]
Kuzin, Maxim [2 ,3 ]
Kane, John M. [1 ,4 ,5 ]
Hiemke, Christoph [6 ,7 ]
Paulzen, Michael [8 ,9 ,10 ]
Haen, Ekkehard [11 ,12 ]
机构
[1] Zucker Hillside Hosp, Psychiat Res, Northwell Hlth, Behav Hlth Pavil,7559 263rd St, Glen Oaks, NY 11004 USA
[2] Univ Zurich, Clienia Schloessli, Private Psychiat Hosp, Zurich, Switzerland
[3] Univ Zurich, Private Psychiat Hosp, Private Psychiat Hosp, Zurich, Switzerland
[4] Zucker Sch Med Hofstra Northwell, Dept Psychiat & Mol Med, Hempstead, NY USA
[5] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA
[6] Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, Mainz, Germany
[7] Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, Mainz, Germany
[8] Alexianer Hosp Aachen, Alexianergraben 33, D-52062 Aachen, Germany
[9] Rhein Westfal TH Aachen, Dept Psychiat Psychotherapy & Psychosomat, Aachen, Germany
[10] JARA, Translat Brain Med, Julich, Germany
[11] Univ Regensburg, Dept Psychiat & Psychotherapy, Clin Pharmacol, Regensburg, Germany
[12] Univ Regensburg, Dept Pharmacol & Toxicol, Regensburg, Germany
关键词
SCHIZOPHRENIA; SERUM; ANTIPSYCHOTICS; SIALORRHEA; PREVALENCE; PNEUMONIA; RESISTANT;
D O I
10.1007/s40262-020-00944-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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-WhitneyUtest 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 < 0.001 for the Mann-WhitneyUtest in both cases). Groups did not differ regarding demographic characteristics except for clozapine daily dose and percentage of smokers (p = 0.005 for the Mann-WhitneyUtest andp = 0.028 for the chi-square test, respectively). There were fewer smokers across patients with hypersalivation compared with patients without and daily doses were higher in patients with hypersalivation. After analysis of covariance, differences remained for both plasma concentrations and concentrations-by-dose (p < 0.001 for both). Post hoc analyses in smokers and non-smokers separately reported similar findings. Conclusions Elevated clozapine plasma concentrations and higher concentrations-by-dose were observed in patients with hypersalivation. A potential role for therapeutic drug monitoring in the prevention or management of clozapine-related hypersalivation is suggested.
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收藏
页码:329 / 335
页数:7
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