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Journal article
The Effect of Body Weight Changes on Total Plasma Clozapine Concentrations Determined by Applying a Statistical Model to the Data From a Double-Blind Trial
Journal of clinical psychopharmacology, v 38(5), pp 442-446
01 Oct 2018
PMID: 30106876
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Purpose/Background Some therapeutic drug monitoring studies suggest that increased weight is associated with small increases in clozapine concentrations. The goal of this study was to reanalyze a US double-blind study using a sophisticated statistical model to test whether weight gains from baseline or increases in percentage of body fat from baseline, computed from a published equation, are associated with increased total plasma clozapine concentrations after controlling for the effects of smoking and sex.
Methods/Procedures Using data from a multidosage randomized double-blind US clozapine trial previously published, a random intercept linear model of steady-state total plasma clozapine concentrations was fitted to 424 concentrations from 47 patients.
Findings/Results After adjusting for sex and smoking, (1) a 1-kg gain in body weight during clozapine treatment was significantly associated with a 1.4% increase in total plasma clozapine concentrations (95% confidence interval = 0.55 to 2.3) and (2) a 1-point increase in percentage of body fat during clozapine treatment was significantly associated with a 5.4% increase in total clozapine concentration (2.5 to 8.3) in females and 1.4% (-1.1 to 4.0) in males.
Implications/Conclusions As hypothesized, weight increases during clozapine treatment, which probably reflect increases in fat tissue, were associated with increases in total plasma concentrations. Pending further replication in other samples, it seems likely that clozapine may deposit in body fat and that this may decrease clozapine clearance. This change may be small in most patients but may be clinically relevant in females with major gains in body fat.
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Details
- Title
- The Effect of Body Weight Changes on Total Plasma Clozapine Concentrations Determined by Applying a Statistical Model to the Data From a Double-Blind Trial
- Creators
- Francisco J. Diaz - University of Kansas Medical CenterRichard C. Josiassen - Translat Neurosci LCC, Conshohocken, PA USAJose de Leon - Eastern State Hosp, Mental Hlth Res Ctr, 1350 Bull Lea Rd, Lexington, KY 40511 USA
- Publication Details
- Journal of clinical psychopharmacology, v 38(5), pp 442-446
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 5
- Grant note
- Novartis Pharmaceuticals Corporation; Novartis MI-145190 / US Public Health Service Grant; United States Department of Health & Human Services; United States Public Health Service National Alliance for Research on Schizophrenia and Depression Established Investigator Award UL1TR000001 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Psychiatry
- Web of Science ID
- WOS:000444241500006
- Scopus ID
- 2-s2.0-85053176215
- Other Identifier
- 991021890007204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy
- Psychiatry