| Effect of bile and lipids on the stereoselective metabolism of halofantrine by rat everted-intestinal sacs. | |
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MedLine Citation:
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PMID: 19496124 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The everted rat intestinal-sac model was utilized to assess the effect of post-prandial conditions on the stereoselective intestinal metabolism of halofantrine to its active metabolite desbutylhalofantrine. Everted intestinal sacs were incubated with (+/-)-halofantrine HCl in the presence of simulated bile solution (containing lecithin, lipase and cholesterol) and lipids to mimic post-prandial conditions in the small intestine. The halofantrine enantiomer concentrations in intestinal sacs were relatively constant in the presence of bile, but decreased significantly on addition of lipids to the incubation media. Formation of desbutylhalofantrine enantiomers was inversely proportional to bile concentration whereas addition of lipids in the presence of bile caused a significant decrease in desbutylhalofantrine:halofantrine ratio of (-) enantiomers. Pre-treatment of rats with peanut oil had no significant effect on desbutylhalofantrine formation in the incubated sacs or microsomal preparations, nor did it affect the expression of intestinal cytochrome P450. Addition of extra cholesterol to the bile incubations caused a significant increase in tissue halofantrine and desbutylhalofantrine concentrations, which as for lower cholesterol, were diminished on addition of other lipids. The results were consistent with previous in vivo evaluations showing that the desbutylhalofantrine to halofantrine ratio was decreased by the ingestion of a high fat meal. |
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Authors:
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Jigar P Patel; Hesham M Korashy; Ayman O S El-Kadi; Dion R Brocks |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chirality Volume: 22 ISSN: 1520-636X ISO Abbreviation: Chirality Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2009-12-28 Completed Date: 2010-05-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8914261 Medline TA: Chirality Country: United States |
Other Details:
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Languages: eng Pagination: 275-83 Citation Subset: IM |
Copyright Information:
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2009 Wiley-Liss, Inc. |
Affiliation:
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Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / metabolism* Cytochrome P-450 Enzyme System / metabolism Intestine, Small / drug effects*, metabolism Intestines / metabolism Lipids / pharmacology* Microsomes, Liver / drug effects* Phenanthrenes / metabolism* Plant Oils Rats Rats, Sprague-Dawley Stereoisomerism |
| Grant Support | |
ID/Acronym/Agency:
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MOP 67169//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Lipids; 0/Phenanthrenes; 0/Plant Oils; 36167-63-2/halofantrine; 8002-03-7/arachis oil; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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