NDLI: Cyclosporine Transfer from Low- and High-Density Lipoproteins Is Partially Influenced by Lipid Transfer Protein I Triglyceride Transfer Activity

Content Provider	Springer Nature Link
Author	Wasan, Kishor M. Subramanian, Ramaswamy Chou, Jenny Wen Lin Ramaswamy, Manisha Pritchard, P. Haydn
Copyright Year	1999
Abstract	Purpose. 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, $^{3}$H-CSA (50 to 1000 ng/ml) was incubated in human plasma for 5 to 120 minutes at 37°C. To determine if LTP I facilitated TG transfer activity regulates the plasma lipoprotein distribution of CSA, $^{3}$H-Triolein (TG)- or $^{3}$H-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 $^{3}$H-Triolein (TG) or $^{3}$H-CSA-free lipoprotein counterpart ± exogenous LTP I (1.0 μg protein/ml) or in delipidated human plasma which contained 1.0 μg protein/ml of endogenous LTP I for 90 minutes at 37°C. These experiments were repeated in the presence of a monoclonal antibody TP1 (15 μg 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 $^{3}$H-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 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 different lipoprotein particles is only partially influenced by LTP I facilitated TG transfer activity.
Starting Page	1067
Ending Page	1073
Page Count	7
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	16
Issue Number	7
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	1999-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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