Kuzin, Maxim and Haen, Ekkehard and Hiemke, Christoph and Bochon, Benjamin and Bochon, Karolina and Gruender, Gerhard and Paulzen, Michael and Schoretsanitis, Georgios (2021) Body mass index as a determinant of clozapine plasma concentrations: A pharmacokinetic-based hypothesis. JOURNAL OF PSYCHOPHARMACOLOGY, 35 (3). pp. 273-278. ISSN 0269-8811, 1461-7285
Full text not available from this repository. (Request a copy)Abstract
Background: Knowledge regarding the impact of body composition measures on pharmacokinetics of antipsychotics is limited. Aims: Our aim was to investigate the impact of body weight and body mass index on clozapine pharmacokinetics using a therapeutic drug monitoring database. Methods: A large therapeutic drug monitoring dataset of clozapine plasma concentrations considering three patient subgroups was analysed: a control group (CLZ(0), 20-30 kg/m(2), n=266), a group with high body mass index (CLZ(high), body mass index > 30 kg/m(2), n=162) and with low body mass index values (CLZ(low), body mass index <20 kg/m(2), n=27). Comparisons of plasma and dose-adjusted plasma concentrations (C/D) of clozapine were based on the Spearman's correlation (rs), Kruskal Wallis and Mann-Whitney-U tests. For percentages we used the Pearson chi-square test (chi(2)). To assess effects of confounders we used bootstrapping analysis of covariates. Results/outcomes: Regarding demographic characteristics, groups differed only for sex percentage with more females than males in CLZ(low) and CLZ(high) compared to CLZ(0) (p=0.001 for chi(2) test). Plasma and C/D values were positively associated with body mass index (rs=0.108, p=0.022 and rs=0.156, p=0.001 respectively). Intergroup differences were observed for plasma and dose-adjusted concentrations of clozapine (p=0.031 and p=0.029 for Kruskal Wallis respectively): post-hoc pairwise comparisons showed higher plasma concentrations and C/D of clozapine in CLZ(high) compared to CLZ(0) (p=0.014 and p=0.007 respectively for Mann-Whitney U-test), by mean 21 and 18%, respectively. Differences for C/D values remained after accounting for sex (p=0.02). Conclusions/interpretation: In obese patients, bioavailability, distribution or elimination of clozapine may be altered due to increased clozapine deposits in fat tissue and hepatic enzyme activity changes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; Therapeutic drug monitoring; clozapine; body mass index; obesity; pharmacokinetics |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Sep 2022 07:27 |
| Last Modified: | 14 Sep 2022 07:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47415 |
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