Plasma protein and lipoprotein distribution of clozapine

Objective: The authors' goal was to determine what effect dyslipidemia has on clozapine's plasma distribution. Method: [H-3]Clozapine plus cold clozapine (335 ng/ml) were incubated in pl asma samples with varying total cholesterol, lipoprotein cholesterol, and t riglyceride concentrations. Following incubation, the plasma was separated into its lipoprotein and lipoprotein-deficient fractions by density gradien t ultracentrifugation and clozapine distribution was determined. Results: Compared with the plasma standard, significantly more clozapine wa s recovered in the very-low-density lipoprotein fraction, which contained e levated 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 shift s from the lipoprotein-deficient fraction to the very-low-density lipoprote in fraction. This redistribution of clozapine may affect the pharmacologica l activity of clozapine.