Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats.
Identifieur interne : 000B66 ( PubMed/Corpus ); précédent : 000B65; suivant : 000B67Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats.
Auteurs : Daryl J. Fediuk ; Tao Wang ; Yufei Chen ; Fiona E. Parkinson ; Michael P. Namaka ; Keith J. Simons ; Frank J. Burczynski ; Xiaochen GuSource :
- Biopharmaceutics & drug disposition [ 1099-081X ] ; 2011.
English descriptors
- KwdEn :
- Administration, Topical, Animals, Area Under Curve, Benzophenones (administration & dosage), Benzophenones (blood), Benzophenones (pharmacokinetics), Cell Line, Tumor, DEET (administration & dosage), DEET (blood), DEET (pharmacokinetics), Half-Life, Injections, Intravenous, Insect Repellents (administration & dosage), Insect Repellents (blood), Insect Repellents (pharmacokinetics), Male, Rats, Rats, Sprague-Dawley, Sunscreening Agents (administration & dosage), Sunscreening Agents (pharmacokinetics).
- MESH :
- chemical , administration & dosage : Benzophenones, DEET, Insect Repellents, Sunscreening Agents.
- chemical , blood : Benzophenones, DEET, Insect Repellents.
- chemical , pharmacokinetics : Benzophenones, DEET, Insect Repellents, Sunscreening Agents.
- Administration, Topical, Animals, Area Under Curve, Cell Line, Tumor, Half-Life, Injections, Intravenous, Male, Rats, Rats, Sprague-Dawley.
Abstract
The insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application.
DOI: 10.1002/bdd.765
PubMed: 21812003
Links to Exploration step
pubmed:21812003Le document en format XML
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Parkinson</name></author><author><name sortKey="Namaka, Michael P" sort="Namaka, Michael P" uniqKey="Namaka M" first="Michael P" last="Namaka">Michael P. Namaka</name></author><author><name sortKey="Simons, Keith J" sort="Simons, Keith J" uniqKey="Simons K" first="Keith J" last="Simons">Keith J. Simons</name></author><author><name sortKey="Burczynski, Frank J" sort="Burczynski, Frank J" uniqKey="Burczynski F" first="Frank J" last="Burczynski">Frank J. Burczynski</name></author><author><name sortKey="Gu, Xiaochen" sort="Gu, Xiaochen" uniqKey="Gu X" first="Xiaochen" last="Gu">Xiaochen Gu</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21812003</idno><idno type="pmid">21812003</idno><idno type="doi">10.1002/bdd.765</idno><idno type="wicri:Area/PubMed/Corpus">000B66</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000B66</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats.</title><author><name sortKey="Fediuk, Daryl J" sort="Fediuk, Daryl J" uniqKey="Fediuk D" first="Daryl J" last="Fediuk">Daryl J. 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Burczynski</name></author><author><name sortKey="Gu, Xiaochen" sort="Gu, Xiaochen" uniqKey="Gu X" first="Xiaochen" last="Gu">Xiaochen Gu</name></author></analytic><series><title level="j">Biopharmaceutics & drug disposition</title><idno type="eISSN">1099-081X</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Topical</term><term>Animals</term><term>Area Under Curve</term><term>Benzophenones (administration & dosage)</term><term>Benzophenones (blood)</term><term>Benzophenones (pharmacokinetics)</term><term>Cell Line, Tumor</term><term>DEET (administration & dosage)</term><term>DEET (blood)</term><term>DEET (pharmacokinetics)</term><term>Half-Life</term><term>Injections, Intravenous</term><term>Insect Repellents (administration & dosage)</term><term>Insect Repellents (blood)</term><term>Insect Repellents (pharmacokinetics)</term><term>Male</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Sunscreening Agents (administration & dosage)</term><term>Sunscreening Agents (pharmacokinetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Benzophenones</term><term>DEET</term><term>Insect Repellents</term><term>Sunscreening Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Benzophenones</term><term>DEET</term><term>Insect Repellents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Benzophenones</term><term>DEET</term><term>Insect Repellents</term><term>Sunscreening Agents</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Topical</term><term>Animals</term><term>Area Under Curve</term><term>Cell Line, Tumor</term><term>Half-Life</term><term>Injections, Intravenous</term><term>Male</term><term>Rats</term><term>Rats, Sprague-Dawley</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21812003</PMID><DateCreated><Year>2011</Year><Month>09</Month><Day>28</Day></DateCreated><DateCompleted><Year>2012</Year><Month>01</Month><Day>17</Day></DateCompleted><DateRevised><Year>2012</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1099-081X</ISSN><JournalIssue CitedMedium="Internet"><Volume>32</Volume><Issue>7</Issue><PubDate><Year>2011</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Biopharmaceutics & drug disposition</Title><ISOAbbreviation>Biopharm Drug Dispos</ISOAbbreviation></Journal><ArticleTitle>Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats.</ArticleTitle><Pagination><MedlinePgn>369-79</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/bdd.765</ELocationID><Abstract><AbstractText>The insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application.</AbstractText><CopyrightInformation>Copyright © 2011 John Wiley & Sons, Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fediuk</LastName><ForeName>Daryl J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>Faculty of Pharmacy, University of Manitoba, Winnipeg, MB R3E0T5, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Tao</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Yufei</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Parkinson</LastName><ForeName>Fiona E</ForeName><Initials>FE</Initials></Author><Author ValidYN="Y"><LastName>Namaka</LastName><ForeName>Michael P</ForeName><Initials>MP</Initials></Author><Author ValidYN="Y"><LastName>Simons</LastName><ForeName>Keith J</ForeName><Initials>KJ</Initials></Author><Author ValidYN="Y"><LastName>Burczynski</LastName><ForeName>Frank J</ForeName><Initials>FJ</Initials></Author><Author ValidYN="Y"><LastName>Gu</LastName><ForeName>Xiaochen</ForeName><Initials>X</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>2005ROP-148547</GrantID><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>08</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Biopharm Drug Dispos</MedlineTA><NlmUniqueID>7911226</NlmUniqueID><ISSNLinking>0142-2782</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001577">Benzophenones</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007302">Insect Repellents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013473">Sunscreening Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>134-62-3</RegistryNumber><NameOfSubstance UI="D003671">DEET</NameOfSubstance></Chemical><Chemical><RegistryNumber>95OOS7VE0Y</RegistryNumber><NameOfSubstance UI="C005290">oxybenzone</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000287" MajorTopicYN="N">Administration, Topical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019540" MajorTopicYN="N">Area Under Curve</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001577" MajorTopicYN="N">Benzophenones</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003671" MajorTopicYN="N">DEET</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006207" MajorTopicYN="N">Half-Life</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007275" MajorTopicYN="N">Injections, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007302" MajorTopicYN="N">Insect Repellents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013473" MajorTopicYN="N">Sunscreening Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName 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