['The purpose of this study was to examine the influence of lipoprotein surface charge on the plasma distribution of cyclosporine A (CSA).', 'Phosphatidylinositol (PI; 40 micromol) was administered intravenously to rabbits. Blood was removed 10 min after injection and plasma was retrieved. Radiolabeled CSA ([3H] CSA) at a concentration of 1000 ng/mL was incubated for 60 min at 37 degrees C in control and PI-treated rabbit plasma. After incubation, plasma was separated into its lipoprotein and lipoprotein-deficient plasma (LPDP) fractions by density gradient ultracentrifugation, and the percentage of [3H]CSA recovered in each fraction was determined by radioactivity. To determine lipoprotein surface charge within control and PI-treated plasma, the zeta potential of each lipoprotein fraction was measured. The effect of PI on lipoprotein surface charge was further confirmed by gel electrophoresis.', 'PI treatment caused low-density lipoprotein (LDL) fraction to migrate further on the agarose gel, indicative of an increased negative surface charge. Zeta potential analysis further showed that LDL particles had a surface potential of -11.4 +/- 1.9 mV and -17.4 +/- 3 mV in control and PI-treated groups, respectively. A greater percentage of [3H]CSA was recovered within the LDL (16.4 +/-1.1% vs. 7.7 +/- 2.1%; n = 3; p < 0.05) fraction after incubation in PI treated than in control plasma, respectively.'] Do modifications in lipoprotein surface charge alter cyclosporine A association with low-density lipoproteins?