Body mass index as a determinant of clozapine plasma concentrations: A pharmacokinetic-based hypothesis.
J Psychopharmacol
; 35(3): 273-278, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33546578
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 (CLZ0, 20-30 kg/m2, n=266), a group with high body mass index (CLZhigh, body mass index ⩾30 kg/m2, n=162) and with low body mass index values (CLZlow, body mass index <20 kg/m2, 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 (χ2). 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 CLZlow and CLZhigh compared to CLZ0 (p=0.001 for χ2 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 CLZhigh compared to CLZ0 (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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antipsicóticos
/
Monitoramento de Medicamentos
/
Clozapina
/
Obesidade
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Psychopharmacol
Ano de publicação:
2021
Tipo de documento:
Article