The influence of dyslipidemia on the plasma protein and lipoprotein distribution of haloperidol.
The objective of this study is to determine the effect of dyslipidemia on the plasma protein and lipoprotein distribution of haloperidol. In doing so, total plasma cholesterol and triglyceride levels were adjusted by adding differing volumes of concentrated low-density lipoproteins and very-low-density lipoproteins to normolipidemic plasma. Following the incubation of [3H]-haloperidol plus cold haloperidol (18 microg/ml) the plasma was separated into its lipoprotein and lipoprotein deficient fractions by density gradient ultra centrifugation and [3H]-haloperidol distribution was determined. Our results revealed a significant positive correlation between total cholesterol concentration and haloperidol recovery in the low-density lipoprotein fraction (r=0.975, df=13, P<0.005). A positive correlation was also observed between total plasma triglyceride concentration and haloperidol recovery from both the very low-density lipoprotein (r=0.965, df=16, P<0.002) and low-density lipoprotein fractions (r=0.935, df=16, P<0.005). This redistribution was the result of haloperidol leaving the lipoprotein-deficient fraction were it is primarily bound to albumin and alpha(1)-acid glycoprotein. This redistribution of haloperidol may influence its clinical efficacy.
Procyshyn
Ric M
RM
Division of Pharmaceutics amd Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada. rprocyshyn@bcmhs.bc.ca
Tsai
Gina
G
Wasan
Kishor M
KM
D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000097:blood / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry; D015243:Cholesterol, VLDL / Q000097:blood / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000493:pharmacokinetics*; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism*; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood / Q000494:pharmacology; D014461:Ultracentrifugation
D001798:Blood Proteins; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D006220:Haloperidol