caa a22 4500 477127088 CHVBK 20180405111653.0 cr unu---uuuuu 170330e19971001xx s 000 0 eng 10.1023/A:1012141309951 doi (NATIONALLICENCE)springer-10.1023/A:1012141309951 Effects of Low and High Density Lipoproteins on Renal Cyclosporine A and Cyclosporine G Disposition in the Isolated Perfused Rat Kidney [Elektronische Daten] [Michelle Strong, Clarence Ueda] Purpose. 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 ∼four-fold lower when compared to controls (∼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. Plenum Publishing Corporation, 1997 renal clearance nationallicence cyclosporine A nationallicence cyclosporine G nationallicence low density lipoprotein nationallicence high density lipoprotein nationallicence isolated perfused kidney nationallicence Strong Michelle Department of Pharmaceutical Sciences, University of Nebraska Medical Center, College of Pharmacy, 600 S. 42nd Street, 68198-6000, Omaha, Nebraska aut Ueda Clarence Department of Pharmaceutical Sciences, University of Nebraska Medical Center, College of Pharmacy, 600 S. 42nd Street, 68198-6000, Omaha, Nebraska aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1466-1471 0724-8741 14:10<1466 1997 14 11095 https://doi.org/10.1023/A:1012141309951 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012141309951 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Strong Michelle Department of Pharmaceutical Sciences, University of Nebraska Medical Center, College of Pharmacy, 600 S. 42nd Street, 68198-6000, Omaha, Nebraska aut NATIONALLICENCE 700 1- Ueda Clarence Department of Pharmaceutical Sciences, University of Nebraska Medical Center, College of Pharmacy, 600 S. 42nd Street, 68198-6000, Omaha, Nebraska aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1466-1471 0724-8741 14:10<1466 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer