EFFECTS OF PLASMA-LIPID LEVELS ON BLOOD DISTRIBUTION AND PHARMACOKINETICS OF CYCLOSPORINE-A

The present study attempted to characterize the distribution of cyclos porin A (CsA) among the lipoprotein fractions, very-low-, intermediate -, low-, and high-density (VLDL, IDL, LDL, and HDL, respectively) in t he plasma of patients awaiting heart transplantation and the influence of plasma lipid constituents on the pharmacokinetics of CsA. Major fr actions of a therapeutic concentration of CsA were found in HDL and in LDL. In addition, plasma lipid concentrations (total cholesterol, tri glycerides, phospholipids, VLDL-cholesterol-TC, TG, PL, VLDLc, respect ively) are positively correlated with the CsA distribution within the LDL fraction, and negatively correlated with the CsA distribution with in the HDL fraction. Thus, the percentage of CsA in each type of lipop roteins was shown to vary with the lipid levels among individuals. A s ignificant negative correlation was found between apparent distributio n volume at steady state (V(ss)) in plasma and TC, PL, and LDLc and be tween the area under the curve measured in blood (AUC(B)) for whole bl ood and PL.