title: Cyclosporine transfer from low- and high-density lipoproteins is partially influenced by lipid transfer protein I triglyceride transfer activity.
abstract: OBJECTIVE
  The purpose of this study was to determine if lipid transfer protein (LTP I) facilitated triglyceride (TG) transfer activity regulates the plasma lipoprotein distribution of cyclosporine (CSA).
  
  
  METHODS
  To assess the influence of drug concentration and incubation time on the plasma lipoprotein distribution of CSA, 3H-CSA (50 to 1000 ng/ml) was incubated in human plasma for 5 to 120 minutes at 37 degrees C. To determine if LTP I facilitated TG transfer activity regulates the plasma lipoprotein distribution of CSA, 3H-Triolein (TG)- or 3H-CSA-enriched high-density lipoproteins (HDL) or low-density lipoproteins (LDL) were incubated in T150 buffer (50 mM Tris-HCl, 150 mM NaCl, 0.02% Sodium Azide, 0.01% Disodium EDTA), pH 7.4 which contained a 3H-Triolein (TG) or 3H-CSA-free lipoprotein counterpart +/- exogenous LTP I (1.0 microg protein/ml) or in delipidated human plasma which contained 1.0 microg protein/ml of endogenous LTP I for 90 minutes at 37 degrees C. These experiments were repeated in the presence of a monoclonal antibody TPI (15 microg protein/ml) directed against LTP I.
  
  
  RESULTS
  No differences in CSA lipoprotein distribution were observed following 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 transfer of CSA from only LDL to HDL was greater in T150 buffer than in human plasma. Furthermore, undetectable 3H-CSA transfer from HDL to LDL in T150 buffer containing purified LTP I was observed. In addition, when the percent transfer of TG and CSA were determined in the presence of TPI, 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 different lipoprotein particles is only partially influenced by LTP I facilitated TG transfer activity.
authors.affiliation: Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada. kwasan@unixg.ubc.ca
authors.forename: K M
authors.initials: KM
authors.lastname: Wasan
authors.forename: R
authors.initials: R
authors.lastname: Subramanian
authors.forename: J W
authors.initials: JW
authors.lastname: Chou
authors.forename: M
authors.initials: M
authors.lastname: Ramaswamy
authors.forename: P H
authors.initials: PH
authors.lastname: Pritchard
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D001692:Biological Transport; D002352:Carrier Proteins / Q000097:blood* / Q000494:pharmacology; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007099:Imipramine / Q000097:blood / Q000493:pharmacokinetics; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D014280:Triglycerides / Q000097:blood*; D014316:Tritium
chemical_list: D018759:Adrenergic Uptake Inhibitors; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; C030363:lipid transfer protein; D014316:Tritium; D016572:Cyclosporine; D007099:Imipramine