| Effect of a high-fat meal on absorption and disposition of lipophilic compounds: the importance of degree of association with triglyceride-rich lipoproteins. | |
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MedLine Citation:
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PMID: 17604610 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Following a high-fat meal, triglyceride-rich lipoproteins (TRL) are assembled in the gut and absorbed via the lymph into the blood circulation, producing a temporal hyperlipidemia. The purpose of this study is to verify the hypothesis that this transient acute postprandial hyperlipidemia affects the pharmacokinetics of lipophilic drugs on both absorption and disposition levels by the same underlying mechanism, namely the association of active lipophilic compounds with TRL in the plasma (disposition) or within the enterocyte (lymphatic transport). This concept was assessed in rats using two model compounds, DDT with high affinity to chylomicrons and diazepam which does not bind to chylomicrons. Oral administration of peanut oil significantly increased the AUC of plasma DDT concentrations following its IV bolus administration in comparison to a water treated group. On the other hand, the AUC of diazepam following IV bolus administration was the same in oil and water treated rats. While DDT is known to have significant lymphatic bioavailability, diazepam has negligible intestinal lymphatic transport (0.014+/-0.004% of a given dose). In conclusion, lipophilic molecules that bind extensively to TRL will be prone to both intestinal lymphatic transport and to post-absorptive changes in disposition (decrease in clearance and volume of distribution) following a high-fat meal. |
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Authors:
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Pavel Gershkovich; Amnon Hoffman |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-18 |
Journal Detail:
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Title: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences Volume: 32 ISSN: 0928-0987 ISO Abbreviation: Eur J Pharm Sci Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-07-31 Completed Date: 2007-10-18 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9317982 Medline TA: Eur J Pharm Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 24-32 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Israel. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Animals Area Under Curve Chlorobenzenes / blood, metabolism, pharmacokinetics* Chylomicrons / chemistry, metabolism DDT Diazepam / blood, metabolism, pharmacokinetics* Dietary Fats / administration & dosage*, metabolism Food-Drug Interactions Injections, Intravenous Intestinal Absorption / drug effects Lipoproteins / chemistry*, metabolism Lipoproteins, VLDL / chemistry, metabolism Lymph / chemistry, metabolism Male Plant Oils / administration & dosage, metabolism Postprandial Period Protein Binding Rats Rats, Wistar Triglycerides / blood, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Chlorobenzenes; 0/Chylomicrons; 0/Dietary Fats; 0/Lipoproteins; 0/Lipoproteins, VLDL; 0/Plant Oils; 0/Triglycerides; 439-14-5/Diazepam; 50-29-3/DDT; 8002-03-7/arachis oil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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