Zusammenfassung
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 ...
Zusammenfassung
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.
Altmetric