Cyclosporine transfer from low- and high-density lipoproteins is partiallyinfluenced by lipid transfer protein I triglyceride transfer activity

Purpose, The purpose of this study was to determine if lipid transfer prote in (LTP I) facilitated triglyceride (TG) transfer activity regulates the pl asma lipoprotein distribution of cyclosporine (CSA). Methods. To assess the influence of drug concentration and incubation time on the plasma lipoprotein distribution of CSA, H-3-CSA (50 to 1000 ng/ml) w as incubated in human plasma for 5 to 120 minutes at 37 degrees C. To deter mine if LTP I facilitated TG transfer activity regulates the plasma lipopro tein distribution of CSA, H-3-Triolein (TG)- or H-3-CSA-enriched high-densi ty lipoproteins (HDL) or low-density lipoproteins (LDL) were incubated in T 150 buffer (50 mM Tris-HCl, 150 mM NaCl, 0.02% Sodium Azide, 0.01% Disodium EDTA), pH 7.4 which contained a H-3-Triolein (TG) or H-3-CSA-free lipoprot ein counter part +/- exogenous LTP I (1.0 mu g protein/ml) or in delipidate d human plasma which contained 1.0 mu g protein/ml of endogenous LTP I for 90 minutes at 37 degrees C. These experiments were repeated in the presence of a monoclonal antibody TP1 (15 mu g protein/ml) directed against LTP I. Results. No differences in CSA lipoprotein distribution were observed follo wing incubation of the drug at varying concentrations and incubation times in human plasma. The percent transfer of TG from HDL to LDL and LDL to HDL was greater in T150 buffer than in human plasma. However, the percent trans fer of CSA from only LDL to HDL was greater in T150 buffer than in human pl asma. Furthermore, undetectable H-3-CSA transfer from HDL to LDL in T150 bu ffer containing purified LTP I was observed. In addition, when the percent transfer of TG and CSA were determined in the presence of TP1, the percent transfer of TG and CSA from only LDL to HDL were significantly decreased in T150 buffer and human plasma compared to controls. Conclusions. These findings suggest that the transfer of CSA between differ ent lipoprotein particles is only partially influenced by LTP I facilitated TG transfer activity.