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Plasma protein and lipoprotein distribution of clozapine
R M Procyshyn1, N B Kennedy, S Marriage
1Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 E. Mall Ave., Vancouver, B.C., Canada V6T 1Z3.
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.