title: Effects of low and high density lipoproteins on renal cyclosporine A and cyclosporine G disposition in the isolated perfused rat kidney.
abstract: OBJECTIVE
  This study investigated the effects of low (LDL) and high density lipoproteins (HDL) on renal cyclosporine A (CsA) and cyclosporine G (CsG) disposition in the isolated perfused rat kidney model.
  
  
  METHODS
  Kidneys were perfused with CsA or CsG in perfusion medium containing 6% protein, bovine serum albumin only (BSA) (Control), LDL (200 mg/dl) and BSA, or HDL (200 mg/dl) and BSA. In vitro protein binding studies were conducted with CsA and CsG in the same media.
  
  
  RESULTS
  The unbound fractions (fu) of CsA and CsG were significantly reduced with LDL and HDL in the perfusion media. In the presence of LDL, fu for CsA and CsG was 3.9% and 5.9%, respectively. With HDL, fu was 2.1% for CsA and 1.8% for CsG. fu for the controls was 14.7% for CsA and 11.9% for CsG. Renal clearance (CLR) of CsA and CsG was significantly reduced when perfused with perfusion medium containing LDL and HDL. LDL and HDL had similar effects on reducing CsA and CsG CLR, and were approximately four-fold lower when compared to controls (approximately 0.006 Vs. 0.023 ml/min). Renal CsA and CsG tissue (whole organ, cortex and medulla) concentrations were lower than corresponding controls when perfused with LDL or HDL.
  
  
  CONCLUSIONS
  The interaction of CsA and CsG with LDL and HDL significantly reduced the CLR and extent of renal tissue distribution of both compounds.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, College of Pharmacy, Omaha 68198-6000, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Strong
authors.forename: C T
authors.initials: CT
authors.lastname: Ueda
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007677:Kidney Function Tests; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D001798:Blood Proteins; D007166:Immunosuppressive Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C045571:cyclosporin G; D016572:Cyclosporine