INFLUENCE OF DIETARY SUBSTANCES ON INTESTINAL DRUG METABOLISM AND TRANSPORT
Identifieur interne : 000A62 ( Pmc/Corpus ); précédent : 000A61; suivant : 000A63INFLUENCE OF DIETARY SUBSTANCES ON INTESTINAL DRUG METABOLISM AND TRANSPORT
Auteurs : Christina S. Won ; Nicholas H. Oberlies ; Mary F. PaineSource :
- Current drug metabolism [ 1389-2002 ] ; 2010.
Abstract
Successful delivery of promising new chemical entities
Url:
PubMed: 21189136
PubMed Central: 3034088
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PMC:3034088Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">INFLUENCE OF DIETARY SUBSTANCES ON INTESTINAL DRUG METABOLISM AND TRANSPORT</title>
<author><name sortKey="Won, Christina S" sort="Won, Christina S" uniqKey="Won C" first="Christina S." last="Won">Christina S. Won</name>
<affiliation><nlm:aff id="A1">Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569 USA</nlm:aff>
</affiliation>
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<author><name sortKey="Oberlies, Nicholas H" sort="Oberlies, Nicholas H" uniqKey="Oberlies N" first="Nicholas H." last="Oberlies">Nicholas H. Oberlies</name>
<affiliation><nlm:aff id="A2">Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402-6170 USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Paine, Mary F" sort="Paine, Mary F" uniqKey="Paine M" first="Mary F." last="Paine">Mary F. Paine</name>
<affiliation><nlm:aff id="A1">Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569 USA</nlm:aff>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">INFLUENCE OF DIETARY SUBSTANCES ON INTESTINAL DRUG METABOLISM AND TRANSPORT</title>
<author><name sortKey="Won, Christina S" sort="Won, Christina S" uniqKey="Won C" first="Christina S." last="Won">Christina S. Won</name>
<affiliation><nlm:aff id="A1">Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569 USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oberlies, Nicholas H" sort="Oberlies, Nicholas H" uniqKey="Oberlies N" first="Nicholas H." last="Oberlies">Nicholas H. Oberlies</name>
<affiliation><nlm:aff id="A2">Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402-6170 USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Paine, Mary F" sort="Paine, Mary F" uniqKey="Paine M" first="Mary F." last="Paine">Mary F. Paine</name>
<affiliation><nlm:aff id="A1">Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569 USA</nlm:aff>
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<series><title level="j">Current drug metabolism</title>
<idno type="ISSN">1389-2002</idno>
<idno type="eISSN">1875-5453</idno>
<imprint><date when="2010">2010</date>
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<front><div type="abstract" xml:lang="en"><p id="P1">Successful delivery of promising new chemical entities <italic>via</italic>
the oral route is rife with challenges, some of which cannot be explained or foreseen during drug development. Further complicating an already multifaceted problem is the obvious, yet often overlooked, effect of dietary substances on drug disposition and response. Some dietary substances, particularly fruit juices, have been shown to inhibit biochemical processes in the intestine, leading to altered pharmacokinetic (PK), and potentially pharmacodynamic (PD), outcomes. Inhibition of intestinal CYP3A-mediated metabolism is the major mechanism by which fruit juices, including grapefruit juice, enhances systemic exposure to new and already marketed drugs. Inhibition of intestinal non-CYP3A enzymes and apically-located transport proteins represent recently identified mechanisms that can alter PK and PD. Several fruit juices have been shown to inhibit these processes <italic>in vitro</italic>
, but some interactions have not translated to the clinic. The lack of <italic>in vitro-in vivo</italic>
concordance is due largely to a lack of rigorous methods to elucidate causative ingredients prior to clinical testing. Identification of specific components and underlying mechanisms is challenging, as dietary substances frequently contain multiple, often unknown, bioactive ingredients that vary in composition and bioactivity. A translational research approach, combining expertise from clinical pharmacologists and natural products chemists, is needed to develop robust models describing PK/PD relationships between a given dietary substance and drug of interest. Validation of these models through well-designed clinical trials would facilitate development of common practice guidelines for managing drug-dietary substance interactions appropriately.</p>
</div>
</front>
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<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">100960533</journal-id>
<journal-id journal-id-type="pubmed-jr-id">21839</journal-id>
<journal-id journal-id-type="nlm-ta">Curr Drug Metab</journal-id>
<journal-title>Current drug metabolism</journal-title>
<issn pub-type="ppub">1389-2002</issn>
<issn pub-type="epub">1875-5453</issn>
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<article-meta><article-id pub-id-type="pmid">21189136</article-id>
<article-id pub-id-type="pmc">3034088</article-id>
<article-id pub-id-type="manuscript">NIHMS268586</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
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<title-group><article-title>INFLUENCE OF DIETARY SUBSTANCES ON INTESTINAL DRUG METABOLISM AND TRANSPORT</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Won</surname>
<given-names>Christina S.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Oberlies</surname>
<given-names>Nicholas H.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Paine</surname>
<given-names>Mary F.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="corresp" rid="CR1">*</xref>
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<aff id="A1"><label>1</label>
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569 USA</aff>
<aff id="A2"><label>2</label>
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402-6170 USA</aff>
<author-notes><corresp id="CR1"><label>*</label>
<bold>Corresponding author:</bold>
Mary F. Paine, RPh, PhD, 2320 Kerr Hall, CB #7569, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569 USA, Tel.: 919-966-9984, Fax: 919-962-0644, <email>mpaine@unc.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>31</day>
<month>1</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><day>1</day>
<month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>11</month>
<year>2011</year>
</pub-date>
<volume>11</volume>
<issue>9</issue>
<fpage>778</fpage>
<lpage>792</lpage>
<abstract><p id="P1">Successful delivery of promising new chemical entities <italic>via</italic>
the oral route is rife with challenges, some of which cannot be explained or foreseen during drug development. Further complicating an already multifaceted problem is the obvious, yet often overlooked, effect of dietary substances on drug disposition and response. Some dietary substances, particularly fruit juices, have been shown to inhibit biochemical processes in the intestine, leading to altered pharmacokinetic (PK), and potentially pharmacodynamic (PD), outcomes. Inhibition of intestinal CYP3A-mediated metabolism is the major mechanism by which fruit juices, including grapefruit juice, enhances systemic exposure to new and already marketed drugs. Inhibition of intestinal non-CYP3A enzymes and apically-located transport proteins represent recently identified mechanisms that can alter PK and PD. Several fruit juices have been shown to inhibit these processes <italic>in vitro</italic>
, but some interactions have not translated to the clinic. The lack of <italic>in vitro-in vivo</italic>
concordance is due largely to a lack of rigorous methods to elucidate causative ingredients prior to clinical testing. Identification of specific components and underlying mechanisms is challenging, as dietary substances frequently contain multiple, often unknown, bioactive ingredients that vary in composition and bioactivity. A translational research approach, combining expertise from clinical pharmacologists and natural products chemists, is needed to develop robust models describing PK/PD relationships between a given dietary substance and drug of interest. Validation of these models through well-designed clinical trials would facilitate development of common practice guidelines for managing drug-dietary substance interactions appropriately.</p>
</abstract>
<kwd-group><kwd>bioavailability</kwd>
<kwd>drug interaction</kwd>
<kwd>food</kwd>
<kwd>fruit juice</kwd>
<kwd>grapefruit juice</kwd>
<kwd>intestine</kwd>
<kwd>metabolism</kwd>
<kwd>transport</kwd>
</kwd-group>
<contract-num rid="GM1">R01 GM077482-04
||GM</contract-num>
<contract-sponsor id="GM1">National Institute of General Medical Sciences : NIGMS</contract-sponsor>
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</front>
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