Cholesteryl ester transfer protein facilitates the movement of water-insoluble drugs between lipoproteins: a novel biological function for a well-characterized lipid transfer protein.
This review article addresses the recently discovered finding that cholesteryl ester transfer protein (CETP) can facilitate the transfer of water-insoluble drugs between different lipoprotein subclasses. This protein, which is often referred to as lipid transfer protein I (LTP I), is involved in the lipid regulation of lipoproteins. It is responsible for the facilitated transfer of core lipoprotein lipids, cholesteryl ester and triglycerides, and approximately one-third of the coat lipoprotein lipid, phosphatidylcholine, between different plasma lipoproteins. The human body appears to recognize exogenous water-insoluble drugs as lipid-like particles, which suggests that these compounds may interact with lipoproteins just like endogenous plasma lipids, and thus their transfer between lipoproteins may be facilitated by plasma CETP. Patients with a variety of diseases (i.e. diabetes, cancer, AIDS) often exhibit hypo- and/or hypercholesterolemia and triglyceridemia, commonly referred to as dyslipidemias, which result in changes in their plasma lipoprotein-lipid composition and concentration. The interaction of water-insoluble drugs with these dyslipidemic lipoproteins may be responsible for the differences seen in the pharmacokinetics and pharmacodynamics of the drug within different diseased patient populations. It is possible that these differences may be linked to the ability of CETP to transfer these compounds from one lipoprotein to another. This review examines the current understanding of the relationship between CETP activity and the lipoprotein distribution of a number of compounds (e.g. amphotericin B and cyclosporine A). It further suggests that additional research will expand our understanding of the role of CETP to explain other functions in lipophilic drug distribution and metabolism.
Kwong
Mona
M
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall Avenue, Vancouver, BC, Canada V6T 1Z3.
Wasan
Kishor M
KM
D000666:Amphotericin B / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism; D016572:Cyclosporine / Q000493:pharmacokinetics*; D006023:Glycoproteins; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D012995:Solubility; D014867:Water / Q000737:chemistry
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008074:Lipoproteins; C030363:lipid transfer protein; D014867:Water; D000666:Amphotericin B; D016572:Cyclosporine