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Am J Psychiatry. 2001 Jun;158(6):949-51.

Plasma protein and lipoprotein distribution of clozapine.

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  • 1Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 E. Mall Ave., Vancouver, B.C., Canada V6T 1Z3.



The authors' goal was to determine what effect dyslipidemia has on clozapine's plasma distribution.


[(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.


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.


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.

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