Role of plasma lipoproteins in modifying the toxic effects of water-insoluble drugs: studies with cyclosporine A.
Lipoproteins are a heterogeneous population of macromolecular aggregates of lipids and proteins that are responsible for the transport of lipids through the vascular and extravascular fluids from their site of synthesis or absorption to peripheral tissues. Lipoproteins are involved in other biological processes as well, including coagulation and tissue repair, and serve as carriers of a number of hydrophobic compounds within the systemic circulation. It has been well documented that disease states (eg, AIDS, diabetes, cancer) significantly influence circulating lipoprotein content and composition. Therefore, it appears possible that changes in the lipoprotein profile would affect not only the ability of a compound to associate with lipoproteins but also the distribution of the compound within the lipoprotein subclasses. Such an effect could alter the pharmacokinetics and pharmacological action of the drug. This paper reviews the factors that influence the interaction of one model hydrophobic compound, cyclosporine A, with lipoproteins and the implications of altered plasma lipoprotein concentrations on the pharmacological behavior of this compound.
Wasan
Kishor M
KM
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Kwasan@interchange.ubc.ca
Ramaswamy
Manisha
M
Kwong
Mona
M
Boulanger
Kathy D
KD
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D012995:Solubility; D014867:Water / Q000737:chemistry
D007166:Immunosuppressive Agents; D008074:Lipoproteins; D014867:Water; D016572:Cyclosporine