Plasma protein and lipoprotein distribution of clozapine.
OBJECTIVE
The authors' goal was to determine what effect dyslipidemia has on clozapine's plasma distribution.


METHODS
[(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.
Procyshyn
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RM
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 E. Mall Ave., Vancouver, B.C., Canada V6T 1Z3.
Kennedy
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NB
Marriage
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Wasan
K M
KM
D014150:Antipsychotic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000097:blood*; D003024:Clozapine / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D014280:Triglycerides / Q000097:blood*
D014150:Antipsychotic Agents; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D003024:Clozapine