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Factors affecting the lipoprotein distribution of cyclosporine : lipoprotein lipid concentration, lipoprotein composition and cholesteryl ester transfer protein activity Wong, Wesley
Abstract
The purpose of this study was to determine factors that influence the lipoprotein distribution of cyclosporine (CSA). Cyclosporine is an immunosuppressant drug that has been effective in preventing graft rejection but the use of cyclosporine is limited by its renal toxicity. The majority of the cyclosporine (-95%) is found in the high density lipoprotein (HDL) and low density lipoprotein (LDL) fractions with the remainder in the very low density lipoprotein fraction (VLDL) following incubation in human plasma. It has been clinically observed that patients with hypertriglyceridemia show decreases in CSA activity while in hypocholesterolemic patients, increases in CSA toxicity occur. Such dyslipidemias represent changes in lipoprotein lipid concentration and composition which may result in changes in the lipoprotein distribution of CSA. We studied such changes and found that as lipid concentration of LDL and VLDL increased, more CSA was found to be associated with this lipoprotein fraction. A parallel decrease in CSA was found to be associated with HDL when the triglyceride concentration of HDL was increased. Another factor that was found to affect the lipoprotein distribution of cyclosporine was cholesteryl ester transfer protein (CETP), which is normally involved in the exchange of cholesteryl ester for triglyceride between HDL and LDL or VLDL. The transfer of CSA from LDL to HDL was shown to be dependent on CETP activity while the reciprocal transfer was independent of CETP. Thus we have demonstrated that the lipoprotein distribution of cyclosporine can be influenced by both lipoprotein lipid composition and the activity of CETP. Because diseased and transplant patients have been shown to have changes in both lipid profile and CETP activity, this may alter the lipoprotein distribution of cyclosporine and possibly alter cyclosporine activity. By monitoring a patient's lipid profile and CETP activity it may be possible to more accurately dose cyclosporine in order to maximize its efficacy while minimizing cyclosporine toxicity.
Item Metadata
Title |
Factors affecting the lipoprotein distribution of cyclosporine : lipoprotein lipid concentration, lipoprotein composition and cholesteryl ester transfer protein activity
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1999
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Description |
The purpose of this study was to determine factors that influence the lipoprotein distribution
of cyclosporine (CSA). Cyclosporine is an immunosuppressant drug that has been effective
in preventing graft rejection but the use of cyclosporine is limited by its renal toxicity. The
majority of the cyclosporine (-95%) is found in the high density lipoprotein (HDL) and low
density lipoprotein (LDL) fractions with the remainder in the very low density lipoprotein
fraction (VLDL) following incubation in human plasma.
It has been clinically observed that patients with hypertriglyceridemia show decreases in
CSA activity while in hypocholesterolemic patients, increases in CSA toxicity occur. Such
dyslipidemias represent changes in lipoprotein lipid concentration and composition which
may result in changes in the lipoprotein distribution of CSA. We studied such changes and
found that as lipid concentration of LDL and VLDL increased, more CSA was found to be
associated with this lipoprotein fraction. A parallel decrease in CSA was found to be
associated with HDL when the triglyceride concentration of HDL was increased.
Another factor that was found to affect the lipoprotein distribution of cyclosporine was
cholesteryl ester transfer protein (CETP), which is normally involved in the exchange of
cholesteryl ester for triglyceride between HDL and LDL or VLDL. The transfer of CSA
from LDL to HDL was shown to be dependent on CETP activity while the reciprocal transfer
was independent of CETP. Thus we have demonstrated that the lipoprotein distribution of cyclosporine can be
influenced by both lipoprotein lipid composition and the activity of CETP. Because diseased
and transplant patients have been shown to have changes in both lipid profile and CETP
activity, this may alter the lipoprotein distribution of cyclosporine and possibly alter
cyclosporine activity. By monitoring a patient's lipid profile and CETP activity it may be
possible to more accurately dose cyclosporine in order to maximize its efficacy while
minimizing cyclosporine toxicity.
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Extent |
5648379 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-06-12
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0099387
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1999-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.