Show simple item record

AuthorPatel, J. P.
AuthorHamdy, D. A.
AuthorEl-kadi, A. O.
AuthorBrocks, D. R.
Available date2015-11-05T13:23:46Z
Publication Date2012
Publication NameChirality
CitationPatel, J. P., Hamdy, D. A., El-kadi, A. O. and Brocks, D. R. (2012), Effect of serum lipoproteins on stereoselective halofantrine metabolism by rat hepatocytes. Chirality, 24: 558�565.
ISSN1520-636X
URIhttp://dx.doi.org/10.1002/chir.22054
URIhttp://hdl.handle.net/10576/3752
AbstractExperimental hyperlipidemia has shown to decrease cytochrome P450 3A4 and 2C11 expression and to increase liver concentrations and the plasma protein binding of halofantrine (HF) enantiomers. The present study examined the effect of hyperlipidemic (HL) serum on the metabolism of HF enantiomers by primary rat hepatocytes. Hepatocytes from normolipidemic (NL) and HL (poloxamer 407 treated) rats were incubated with rac-HF in cell media with or without additional rat serum (5%). In those incubations with rat serum, the hepatocytes were preincubated or coincubated with serum from NL or HL rats. Rat serum-free hepatocyte incubations served as controls. Stereospecific assays were used to measure HF and desbutylhalofantrine (its major metabolite) enantiomer concentrations in whole well contents (cells?+?media). Concentrations of desbutylhalofantrine were not measurable. The disappearance (apparent metabolism) of (?)-HF exceeded that of antipode, but HF metabolism did not differ between hepatocytes from NL and HL rats. Coincubation of HL rat serum with NL hepatocytes caused a significant decrease in the disappearance of (?)-HF, whereas in HL hepatocytes, a substantially decreased apparent metabolism was noted for both enantiomers. Compared with NL serum, (?)-HF disappearance was significantly lowered upon preincubation of NL hepatocytes with HL serum. A combination of factors including diminished drug metabolizing or lipoprotein receptor expression, and increased plasma protein binding in the wells, may have contributed to a decrease in apparent metabolism of the HF enantiomers in the presence of lipoproteins from HL rat serum.
SponsorCanadian Institute of Health Research. Grant Number: MOP 87395
Languageen
PublisherJohn Wiley & Sons, Ltd
Subjectantimalarials
Subjecthyperlipidemia
Subjectpharmacokinetics
Subjectclearance
Subjecttriglyceride
Subjectcholesterol
Subjectpoloxamer 407
Subjectdrug metabolism
TitleEffect of serum lipoproteins on stereoselective halofantrine metabolism by rat hepatocytes
TypeArticle
Issue Number7
Volume Number24


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record