R M Procyshyn1, N B Kennedy, S Marriage, K M Wasan. 1. Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 E. Mall Ave., Vancouver, B.C., Canada V6T 1Z3.
Abstract
OBJECTIVE: The authors' goal was to determine what effect dyslipidemia has on clozapine's plasma distribution. METHOD: [(3)H]Clozapine plus cold clozapine (335 ng/ml) were incubated in plasma samples with varying total cholesterol, lipoprotein cholesterol, and triglyceride concentrations. Following incubation, the plasma was separated into its lipoprotein and lipoprotein-deficient fractions by density gradient ultracentrifugation and clozapine distribution was determined. RESULTS: Compared with the plasma standard, significantly more clozapine was recovered in the very-low-density lipoprotein fraction, which contained elevated total cholesterol and triglycerides. Correlation analysis revealed a positive correlation between total plasma triglyceride concentration and clozapine recovery in this fraction. CONCLUSIONS: In plasma samples with elevated triglycerides, clozapine shifts from the lipoprotein-deficient fraction to the very-low-density lipoprotein fraction. This redistribution of clozapine may affect the pharmacological activity of clozapine.
OBJECTIVE: The authors' goal was to determine what effect dyslipidemia has on clozapine's plasma distribution. METHOD: [(3)H]Clozapine plus cold clozapine (335 ng/ml) were incubated in plasma samples with varying total cholesterol, lipoprotein cholesterol, and triglyceride concentrations. Following incubation, the plasma was separated into its lipoprotein and lipoprotein-deficient fractions by density gradient ultracentrifugation and clozapine distribution was determined. RESULTS: Compared with the plasma standard, significantly more clozapine was recovered in the very-low-density lipoprotein fraction, which contained elevated total cholesterol and triglycerides. Correlation analysis revealed a positive correlation between total plasma triglyceride concentration and clozapine recovery in this fraction. CONCLUSIONS: In plasma samples with elevated triglycerides, clozapine shifts from the lipoprotein-deficient fraction to the very-low-density lipoprotein fraction. This redistribution of clozapine may affect the pharmacological activity of clozapine.
Authors: Ric M Procyshyn; Kishor M Wasan; Allen E Thornton; Alasdair M Barr; Eric Y H Chen; Edith Pomarol-Clotet; Emmanuel Stip; Richard Williams; G William Macewan; C Laird Birmingham; William G Honer Journal: J Psychiatry Neurosci Date: 2007-09 Impact factor: 6.186
Authors: Jose de Leon; Can-Jun Ruan; Georgios Schoretsanitis; Carlos De Las Cuevas Journal: Psychother Psychosom Date: 2020-04-14 Impact factor: 17.659