The effects of competitive displacement on haloperidol's plasma distribution in normolipidemic and hyperlipidemic plasma.
OBJECTIVE
To assess whether dyslipidemia affects haloperidol's overall plasma distribution when it is in the presence of another highly protein bound drug that competes for plasma protein binding sites.


METHODS
We performed in vitro studies in which warfarin sodium was pre-incubated in normolipidemic and hyperlipidemic plasma samples in varying concentrations. Following the pre-incubation with warfarin, [3H]-haloperidol mixed with unlabeled haloperidol was added to the plasma samples. The plasma was separated into its lipoprotein and lipoprotein deficient fractions by density gradient ultracentrifugation and haloperidol distribution was determined.


RESULTS
Our results indicate that when normolipidemic plasma was pre-incubated with various concentrations of warfarin no significant redistribution of haloperidol was noted among the various plasma lipoprotein fractions. However, in the case of the hyperlipidemic plasma, pre-incubating with warfarin did result in a significant redistribution of haloperidol from the lipoprotein-deficient fraction to the very-low-density and low-density fractions of lipoproteins.


CONCLUSIONS
Understanding how plasma lipoproteins influence competitive displacement interactions would be valuable in helping to explain and perhaps predict pharmacokinetic parameters that may affect clinical outcome. The clinical significance of competitive displacement of drugs in patients with dyslipidemia requires further study.
Procyshyn
Ric M
RM
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Ho
Tiffany
T
Wasan
Kishor M
KM
D000925:Anticoagulants / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000097:blood*; D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism*; D006220:Haloperidol / Q000097:blood*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000172:deficiency; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D014859:Warfarin / Q000494:pharmacology
D000925:Anticoagulants; D014150:Antipsychotic Agents; D001798:Blood Proteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014859:Warfarin; D006220:Haloperidol