Lipoprotein distribution of a novel endotoxin antagonist, E5531, in plasma from human subjects with various lipid levels.
The purpose of this study was to determine the distribution profile of a novel endotoxin antagonist, [(14)C]E5531, at 1 microg/ml in plasma samples obtained from fasted human subjects with various lipid and protein concentrations. Our findings suggest that the majority of E5531 binds with high-density lipoproteins (HDLs) independently of plasma lipid and protein levels tested. Furthermore, it appears that an increase in triglyceride-rich lipoprotein (TRL) lipid and protein levels and an increase in low-density lipoprotein (LDL) lipid levels significantly increase TRL plus LDL binding of E5531. However, only an increase in HDL protein levels significantly increases HDL binding of E5531.
Wasan
K M
KM
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Kwasan@unixg.ubc.ca
Strobel
F W
FW
Parrott
S C
SC
Lynn
M
M
Christ
W J
WJ
Hawkins
L D
LD
Rossignol
D P
DP
D004731:Endotoxins / Q000037:antagonists & inhibitors*; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D004731:Endotoxins; D008050:Lipid A; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; C092845:E 5531