Absorption, distribution and excretion of 14C‐levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin‐related radioactivity to melanin in vivo
Identifieur interne : 000214 ( Istex/Corpus ); précédent : 000213; suivant : 000215Absorption, distribution and excretion of 14C‐levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin‐related radioactivity to melanin in vivo
Auteurs : Makoto Tanaka ; Chiho Ono ; Masayoshi YamadaSource :
- Journal of Pharmacy and Pharmacology [ 0022-3573 ] ; 2004-04.
English descriptors
- Teeft :
- Albino, Albino rats, Binding characteristics, Binding mechanisms, Chloroquine, Dosing, Electrostatic forces, Excretion, Feces, Fluoroquinolones, Hemihydrate, High affinity, Higher concentrations, Important role, Larsson, Larsson tjalve, Levofloxacin, Levofloxacin hemihydrate, Limited extent, Male rats, Melanin, Melanin binding, Neutral phosphate buffer, Ocular, Ocular pharmacokinetics, Ocular tissues, Ocular toxicity, Pharmacol, Phosphate buffer, Radioactivity, Radioactivity concentrations, Rat, Serum concentrations, Stepien wilczok, Synthetic melanin, Tanaka, Tjalve, Total radioactivity, Toxicity, Unchanged levofloxacin, Urine, Uveal, Uveal tract, Uveal tract extracts, Uveal tract radioactivity concentrations, Uveal tracts, Waals.
Abstract
After single oral administration of 14C‐levofloxacin at a dose of 20 mg kg−1 under non‐fasting conditions, the absorption, distribution and excretion of radioactivity were studied in albino and pigmented rats. Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin‐containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug‐related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (Cmax) of 26.33 + 0.75 μg eq.g−1 at 24 h after dosing and declined slowly with a terminal half‐life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73 + 0.12 μg eq.g−1, which is c. 1/36 of Cmax. The AUC0‐∞ for the uveal tract was 12.58 mg h−1 g−1. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1m HCl/EtOH (30:70), successively. In pigmented rats, approximately 85–48% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1m HCl/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and/or its metabolites with melanin‐containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half‐life of radioactivity in the uveal tract after dosing of 14C‐levofloxacin were found to be much lower and shorter than those after dosing of 14C‐chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin‐containing ocular tissues and shorter duration of therapy compared to chloroquine.
Url:
DOI: 10.1211/0022357023141
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ISTEX:736ADC27AC9E09F8B8F9FE86A601C97A5C0DEEDBLe document en format XML
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Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: tanak6m1@daiichipharm.co.jp</mods:affiliation></affiliation></author><author><name sortKey="Ono, Chiho" sort="Ono, Chiho" uniqKey="Ono C" first="Chiho" last="Ono">Chiho Ono</name><affiliation><mods:affiliation>Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</mods:affiliation></affiliation></author><author><name sortKey="Yamada, Masayoshi" sort="Yamada, Masayoshi" uniqKey="Yamada M" first="Masayoshi" last="Yamada">Masayoshi Yamada</name><affiliation><mods:affiliation>Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. 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Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin‐containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug‐related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (Cmax) of 26.33 + 0.75 μg eq.g−1 at 24 h after dosing and declined slowly with a terminal half‐life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73 + 0.12 μg eq.g−1, which is c. 1/36 of Cmax. The AUC0‐∞ for the uveal tract was 12.58 mg h−1 g−1. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1m HCl/EtOH (30:70), successively. In pigmented rats, approximately 85–48% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1m HCl/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and/or its metabolites with melanin‐containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half‐life of radioactivity in the uveal tract after dosing of 14C‐levofloxacin were found to be much lower and shorter than those after dosing of 14C‐chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin‐containing ocular tissues and shorter duration of therapy compared to chloroquine.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>uveal</json:string><json:string>albino</json:string><json:string>dosing</json:string><json:string>melanin</json:string><json:string>levofloxacin</json:string><json:string>uveal tract</json:string><json:string>chloroquine</json:string><json:string>albino rats</json:string><json:string>tanaka</json:string><json:string>radioactivity</json:string><json:string>radioactivity concentrations</json:string><json:string>tjalve</json:string><json:string>binding characteristics</json:string><json:string>larsson</json:string><json:string>feces</json:string><json:string>toxicity</json:string><json:string>phosphate buffer</json:string><json:string>fluoroquinolones</json:string><json:string>pharmacol</json:string><json:string>ocular tissues</json:string><json:string>hemihydrate</json:string><json:string>waals</json:string><json:string>excretion</json:string><json:string>uveal tract extracts</json:string><json:string>uveal tracts</json:string><json:string>melanin binding</json:string><json:string>serum concentrations</json:string><json:string>electrostatic forces</json:string><json:string>rat</json:string><json:string>larsson tjalve</json:string><json:string>ocular toxicity</json:string><json:string>binding mechanisms</json:string><json:string>important role</json:string><json:string>high affinity</json:string><json:string>ocular</json:string><json:string>urine</json:string><json:string>levofloxacin hemihydrate</json:string><json:string>higher concentrations</json:string><json:string>ocular pharmacokinetics</json:string><json:string>total radioactivity</json:string><json:string>synthetic melanin</json:string><json:string>male rats</json:string><json:string>limited extent</json:string><json:string>uveal tract radioactivity concentrations</json:string><json:string>neutral phosphate buffer</json:string><json:string>unchanged levofloxacin</json:string><json:string>stepien wilczok</json:string></teeft></keywords><author><json:item><name>Makoto Tanaka</name><affiliations><json:string>Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. 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Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</json:string></affiliations></json:item></author><articleId><json:string>JPHP2631</json:string></articleId><arkIstex>ark:/67375/WNG-WRTCNQ19-3</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>After single oral administration of 14C‐levofloxacin at a dose of 20 mg kg−1 under non‐fasting conditions, the absorption, distribution and excretion of radioactivity were studied in albino and pigmented rats. Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin‐containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug‐related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (Cmax) of 26.33 + 0.75 μg eq.g−1 at 24 h after dosing and declined slowly with a terminal half‐life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73 + 0.12 μg eq.g−1, which is c. 1/36 of Cmax. The AUC0‐∞ for the uveal tract was 12.58 mg h−1 g−1. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1m HCl/EtOH (30:70), successively. In pigmented rats, approximately 85–48% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1m HCl/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and/or its metabolites with melanin‐containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half‐life of radioactivity in the uveal tract after dosing of 14C‐levofloxacin were found to be much lower and shorter than those after dosing of 14C‐chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin‐containing ocular tissues and shorter duration of therapy compared to chloroquine.</abstract><qualityIndicators><score>9.636</score><pdfWordCount>4636</pdfWordCount><pdfCharCount>28520</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>7</pdfPageCount><pdfPageSize>572.598 x 778.677 pts</pdfPageSize><pdfWordsPerPage>662</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>true</refBibsNative><abstractWordCount>304</abstractWordCount><abstractCharCount>1976</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Absorption, distribution and excretion of 14C‐levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin‐related radioactivity to melanin in vivo</title><pmid><json:string>15099441</json:string></pmid><genre><json:string>article</json:string></genre><host><title>Journal of Pharmacy and Pharmacology</title><language><json:string>unknown</json:string></language><doi><json:string>10.1111/(ISSN)2042-7158</json:string></doi><issn><json:string>0022-3573</json:string></issn><eissn><json:string>2042-7158</json:string></eissn><publisherId><json:string>JPHP</json:string></publisherId><volume>56</volume><issue>4</issue><pages><first>463</first><last>469</last><total>7</total></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2004</json:string></date><geogName></geogName><orgName><json:string>Aloka Co.</json:string><json:string>Daiichi Pharmaceutical Co.</json:string><json:string>Packard Instrument Company</json:string><json:string>Brinkmann Co.</json:string><json:string>Funabashi Farm Co.</json:string><json:string>Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co</json:string><json:string>Charles River Japan Inc</json:string><json:string>Ltd</json:string><json:string>Daiichi Pure Chemicals Co.</json:string><json:string>Japan Makoto Tanaka, Chiho Ono, Masayoshi Yamada Correspondence</json:string><json:string>Japan SLC Inc</json:string><json:string>Use Committee of Daiichi Pharmaceutical Co</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Levofloxacin</json:string><json:string>Brain Skin</json:string></persName><placeName><json:string>Switzerland</json:string><json:string>Shizuoka</json:string><json:string>Japan</json:string><json:string>Chiba</json:string><json:string>Tokyo</json:string><json:string>Osaka</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Leblanc et al 1998</json:string><json:string>Salazar-Bookaman et al 1994</json:string><json:string>Larsson 1993</json:string><json:string>Tanaka et al</json:string><json:string>Lindquist & Ullberg 1972</json:string><json:string>Fukuda & Sasaki 1989, 1990</json:string><json:string>Ono & Tanaka 2003</json:string><json:string>Tanaka et al 1993</json:string><json:string>Kasuya et al 1976</json:string><json:string>Hurst et al 2002</json:string><json:string>È Tjalve et al 1981</json:string><json:string>Kurata et al 1991</json:string><json:string>Leblanc et al</json:string><json:string>Stepien & Wilczok 1982</json:string><json:string>Goldman & Preston 1957</json:string><json:string>Boke et al 1967</json:string><json:string>Larsson & Tjalve 1979</json:string><json:string>Ono et al 2003</json:string><json:string>Fukuda et al 2000</json:string><json:string>Ings 1984</json:string><json:string>Jones 1999</json:string><json:string>Siefert et al 1999</json:string><json:string>Hobbs et al 1959</json:string><json:string>Tjalve et al 1981</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-WRTCNQ19-3</json:string></ark><categories><wos><json:string>1 - 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<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract xml:lang="en" style="main"><head>ABSTRACT</head><p>After single oral administration of <hi rend="superscript">14</hi>C‐levofloxacin at a dose of 20 mg kg<hi rend="superscript">−1</hi> under non‐fasting conditions, the absorption, distribution and excretion of radioactivity were studied in albino and pigmented rats. Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin‐containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug‐related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (C<hi rend="subscript">max</hi>) of 26.33 + 0.75 μg eq.g<hi rend="superscript">−1</hi> at 24 h after dosing and declined slowly with a terminal half‐life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73 + 0.12 μg eq.g<hi rend="superscript">−1</hi>, which is c. 1/36 of C<hi rend="subscript">max</hi>. The AUC<hi rend="subscript">0‐∞</hi> for the uveal tract was 12.58 mg h<hi rend="superscript">−1</hi> g<hi rend="superscript">−1</hi>. The uveal tracts separated from one eye of each rat were extracted with 0.067 <hi rend="smallCaps">m</hi> phosphate buffer (pH 7.4) and 1<hi rend="smallCaps">m</hi> HCl/EtOH (30:70), successively. In pigmented rats, approximately 85–48% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1<hi rend="smallCaps">m</hi> HCl/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and/or its metabolites with melanin‐containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half‐life of radioactivity in the uveal tract after dosing of <hi rend="superscript">14</hi>C‐levofloxacin were found to be much lower and shorter than those after dosing of <hi rend="superscript">14</hi>C‐chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin‐containing ocular tissues and shorter duration of therapy compared to chloroquine.</p></abstract><textClass><keywords rend="tocHeading1"><term>Original Article</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-WRTCNQ19-3/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)2042-7158</doi><issn type="print">0022-3573</issn><issn type="electronic">2042-7158</issn><idGroup><id type="product" value="JPHP"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="JOURNAL OF PHARMACY AND PHARMACOLOGY">Journal of Pharmacy and Pharmacology</title></titleGroup></publicationMeta><publicationMeta level="part" position="04004"><doi origin="wiley">10.1111/jphp.2004.56.issue-4</doi><numberingGroup><numbering type="journalVolume" number="56">56</numbering><numbering type="journalIssue" number="4">4</numbering></numberingGroup><coverDate startDate="2004-04">April 2004</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="6" status="forIssue"><doi origin="wiley">10.1211/0022357023141</doi><idGroup><id type="unit" value="JPHP2631"></id></idGroup><countGroup><count type="pageTotal" number="7"></count></countGroup><titleGroup><title type="tocHeading1">Original Article</title></titleGroup><copyright>2004 Royal Pharmaceutical Society of Great Britain</copyright><eventGroup><event type="firstOnline" date="2010-02-18"></event><event type="publishedOnlineFinalForm" date="2010-02-18"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.5 mode:FullText source:HeaderRef result:HeaderRef" date="2010-04-06"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-01"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-30"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="463">463</numbering><numbering type="pageLast" number="469">469</numbering></numberingGroup><correspondenceTo><sup>2</sup>Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan. E‐mail: <email>tanak6m1@daiichipharm.co.jp</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:JPHP.JPHP2631.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received September 01, 2003 Accepted January 07, 2004</unparsedEditorialHistory><countGroup><count type="referenceTotal" number="22"></count><count type="linksCrossRef" number="4"></count></countGroup><titleGroup><title type="main">Absorption, distribution and excretion of <sup>14</sup>C‐levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin‐related radioactivity to melanin in vivo</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1" corresponding="yes"><personName><givenNames>Makoto</givenNames><familyName>Tanaka</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>Chiho</givenNames><familyName>Ono</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>Masayoshi</givenNames><familyName>Yamada</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="JP"><unparsedAffiliation>Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">ABSTRACT</title><p>After single oral administration of <sup>14</sup>C‐levofloxacin at a dose of 20 mg kg<sup>−1</sup> under non‐fasting conditions, the absorption, distribution and excretion of radioactivity were studied in albino and pigmented rats. Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin‐containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug‐related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (C<sub>max</sub>) of 26.33 + 0.75 μg eq.g<sup>−1</sup> at 24 h after dosing and declined slowly with a terminal half‐life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73 + 0.12 μg eq.g<sup>−1</sup>, which is c. 1/36 of C<sub>max</sub>. The AUC<sub>0‐∞</sub> for the uveal tract was 12.58 mg h<sup>−1</sup> g<sup>−1</sup>. The uveal tracts separated from one eye of each rat were extracted with 0.067 <sc>m</sc> phosphate buffer (pH 7.4) and 1<sc>m</sc> HCl/EtOH (30:70), successively. In pigmented rats, approximately 85–48% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1<sc>m</sc> HCl/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and/or its metabolites with melanin‐containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half‐life of radioactivity in the uveal tract after dosing of <sup>14</sup>C‐levofloxacin were found to be much lower and shorter than those after dosing of <sup>14</sup>C‐chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin‐containing ocular tissues and shorter duration of therapy compared to chloroquine.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Absorption, distribution and excretion of 14C‐levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin‐related radioactivity to melanin in vivo</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Absorption, distribution and excretion of 14C‐levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin‐related radioactivity to melanin in vivo</title></titleInfo><name type="personal"><namePart type="given">Makoto</namePart><namePart type="family">Tanaka</namePart><affiliation>Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</affiliation><affiliation>E-mail: tanak6m1@daiichipharm.co.jp</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chiho</namePart><namePart type="family">Ono</namePart><affiliation>Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Masayoshi</namePart><namePart type="family">Yamada</namePart><affiliation>Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2004-04</dateIssued><edition>Received September 01, 2003 Accepted January 07, 2004</edition><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="references">22</extent><extent unit="linksCrossRef">4</extent></physicalDescription><abstract lang="en">After single oral administration of 14C‐levofloxacin at a dose of 20 mg kg−1 under non‐fasting conditions, the absorption, distribution and excretion of radioactivity were studied in albino and pigmented rats. Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin‐containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug‐related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (Cmax) of 26.33 + 0.75 μg eq.g−1 at 24 h after dosing and declined slowly with a terminal half‐life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73 + 0.12 μg eq.g−1, which is c. 1/36 of Cmax. The AUC0‐∞ for the uveal tract was 12.58 mg h−1 g−1. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1m HCl/EtOH (30:70), successively. In pigmented rats, approximately 85–48% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1m HCl/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and/or its metabolites with melanin‐containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half‐life of radioactivity in the uveal tract after dosing of 14C‐levofloxacin were found to be much lower and shorter than those after dosing of 14C‐chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin‐containing ocular tissues and shorter duration of therapy compared to chloroquine.</abstract><relatedItem type="host"><titleInfo><title>Journal of Pharmacy and Pharmacology</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">0022-3573</identifier><identifier type="eISSN">2042-7158</identifier><identifier type="DOI">10.1111/(ISSN)2042-7158</identifier><identifier type="PublisherID">JPHP</identifier><part><date>2004</date><detail type="volume"><caption>vol.</caption><number>56</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>463</start><end>469</end><total>7</total></extent></part></relatedItem><relatedItem type="references" displayLabel="cit1"><titleInfo><title>Zur Frage der Chloroquinschädigung des Auges</title></titleInfo><name type="personal"><namePart type="given">W.</namePart><namePart type="family">Böke</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.</namePart><namePart type="family">Bäumer</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">W.</namePart><namePart type="family">Müller‐Limmroth</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Mludeck</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Böke, W., Bäumer, A., Müller‐Limmroth, W., Mludeck, M. 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