Absorption, distribution and excretion of 14C‐chloroquine after single oral administration in albino and pigmented rats: binding characteristics of chloroquine‐related radioactivity to melanin in‐vivo
Identifieur interne : 000209 ( Istex/Corpus ); précédent : 000208; suivant : 000210Absorption, distribution and excretion of 14C‐chloroquine after single oral administration in albino and pigmented rats: binding characteristics of chloroquine‐related radioactivity to melanin in‐vivo
Auteurs : Chiho Ono ; Masayoshi Yamada ; Makoto TanakaSource :
- Journal of Pharmacy and Pharmacology [ 0022-3573 ] ; 2003-12.
English descriptors
- Teeft :
- Albino, Albino rats, Binding characteristics, Binding mechanisms, Chloroquine, Chloroquine diphosphate, Corpus vitreum, Critical role, Diphosphate, Distinct affinity, Dosing, Electrostatic interaction, Equiv, Excretion, Excretion pattern, Faeces, High affinity, Important role, Larsson, Larsson tjalve, Lindquist ullberg, Lower limit, Maximum value, Melanin, Neutral phosphate buffer, Ocular, Ocular tissues, Oral dosing, Phosphate buffer, Radioactivity, Radioactivity concentrations, Rat, Serum concentrations, Stepien wilczok, Strong binding, Synthetic melanin, Tanaka, Testis, Tjalve, Total radioactivity, Urine, Uveal, Uveal tract, Uveal tract concentrations, Uveal tract radioactivity concentrations, Uveal tracts, Vitreum.
Abstract
Chloroquine is an antimalarial agent that has been reported to have distinct affinity to melanin. After single oral administration of 14C‐chloroquine at a dose of 20 mg kg−1 under non‐fasting conditions, the absorption, distribution and excretion of 14C‐chloroquine‐related radioactivity were studied in albino and pigmented rats. The objectives of the study were to investigate differences in the disposition of chloroquine between albino and pigmented rats and to define its in‐vivo binding characteristics to melanin‐containing ocular tissues. Extensive uptake of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there was no quantitative differences in the distribution of radioactivity found between albino and pigmented rats except for melanin‐containing tissues, such as the uveal tract of the eye and perhaps hair follicles. There was selective and strong binding of drug‐related compounds to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value of 158.42 + 7.86 μg equiv g−1 (mean + s.e.) at 1 week and decreased very slowly with a terminal half life of 4476h (187 day). The uveal tract concentrations at 24 weeks were still high (67.75 + 6.19 μg equiv g−1). The AUC for uveal tract was 842.3 mg h g−1. A relatively high concentration was still determined in the uveal tract even at 48 weeks after single oral dosing by whole‐body autoradiography. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1 m HCl–EtOH (30:70) successively. In pigmented rats, almost all radioactivity was released from the tissue with 1 m HCl–EtOH (30:70), indicating that the strong binding by melanin was reversible, and that hydrophobic or electrostatic interaction would play a critical role in the binding of chloroquine and its metabolites with the melanin‐containing ocular tissues. Approximately 70% of the radioactivity given was recovered in urine and faeces up to 144h after dosing both in pigmented and albino rats. The excretion pattern in pigmented rats was similar to that seen in albino rats.
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DOI: 10.1211/0022357022340
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ISTEX:074F7E16AA37A79EFD60DB54E18B9DCD5817ED2ALe document en format XML
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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. Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tanaka, Makoto" sort="Tanaka, Makoto" uniqKey="Tanaka M" first="Makoto" last="Tanaka">Makoto Tanaka</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><affiliation><mods:affiliation>E-mail: tanak6m1@daiichipharm.co.jp</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Pharmacy and Pharmacology</title><title level="j" type="alt">JOURNAL OF PHARMACY AND PHARMACOLOGY</title><idno type="ISSN">0022-3573</idno><idno type="eISSN">2042-7158</idno><imprint><biblScope unit="vol">55</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1647">1647</biblScope><biblScope unit="page" to="1654">1654</biblScope><biblScope unit="page-count">8</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2003-12">2003-12</date></imprint><idno type="ISSN">0022-3573</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3573</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Albino</term><term>Albino rats</term><term>Binding characteristics</term><term>Binding mechanisms</term><term>Chloroquine</term><term>Chloroquine diphosphate</term><term>Corpus vitreum</term><term>Critical role</term><term>Diphosphate</term><term>Distinct affinity</term><term>Dosing</term><term>Electrostatic interaction</term><term>Equiv</term><term>Excretion</term><term>Excretion pattern</term><term>Faeces</term><term>High affinity</term><term>Important role</term><term>Larsson</term><term>Larsson tjalve</term><term>Lindquist ullberg</term><term>Lower limit</term><term>Maximum value</term><term>Melanin</term><term>Neutral phosphate buffer</term><term>Ocular</term><term>Ocular tissues</term><term>Oral dosing</term><term>Phosphate buffer</term><term>Radioactivity</term><term>Radioactivity concentrations</term><term>Rat</term><term>Serum concentrations</term><term>Stepien wilczok</term><term>Strong binding</term><term>Synthetic melanin</term><term>Tanaka</term><term>Testis</term><term>Tjalve</term><term>Total radioactivity</term><term>Urine</term><term>Uveal</term><term>Uveal tract</term><term>Uveal tract concentrations</term><term>Uveal tract radioactivity concentrations</term><term>Uveal tracts</term><term>Vitreum</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Chloroquine is an antimalarial agent that has been reported to have distinct affinity to melanin. After single oral administration of 14C‐chloroquine at a dose of 20 mg kg−1 under non‐fasting conditions, the absorption, distribution and excretion of 14C‐chloroquine‐related radioactivity were studied in albino and pigmented rats. The objectives of the study were to investigate differences in the disposition of chloroquine between albino and pigmented rats and to define its in‐vivo binding characteristics to melanin‐containing ocular tissues. Extensive uptake of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there was no quantitative differences in the distribution of radioactivity found between albino and pigmented rats except for melanin‐containing tissues, such as the uveal tract of the eye and perhaps hair follicles. There was selective and strong binding of drug‐related compounds to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value of 158.42 + 7.86 μg equiv g−1 (mean + s.e.) at 1 week and decreased very slowly with a terminal half life of 4476h (187 day). The uveal tract concentrations at 24 weeks were still high (67.75 + 6.19 μg equiv g−1). The AUC for uveal tract was 842.3 mg h g−1. A relatively high concentration was still determined in the uveal tract even at 48 weeks after single oral dosing by whole‐body autoradiography. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1 m HCl–EtOH (30:70) successively. In pigmented rats, almost all radioactivity was released from the tissue with 1 m HCl–EtOH (30:70), indicating that the strong binding by melanin was reversible, and that hydrophobic or electrostatic interaction would play a critical role in the binding of chloroquine and its metabolites with the melanin‐containing ocular tissues. Approximately 70% of the radioactivity given was recovered in urine and faeces up to 144h after dosing both in pigmented and albino rats. 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Ltd, 16–13, Kita‐Kasai 1‐Chome, Edogawa‐ku, Tokyo 134–8630, Japan</json:string><json:string>E-mail: tanak6m1@daiichipharm.co.jp</json:string></affiliations></json:item></author><articleId><json:string>JPHP2471</json:string></articleId><arkIstex>ark:/67375/WNG-4L384X5G-S</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Chloroquine is an antimalarial agent that has been reported to have distinct affinity to melanin. After single oral administration of 14C‐chloroquine at a dose of 20 mg kg−1 under non‐fasting conditions, the absorption, distribution and excretion of 14C‐chloroquine‐related radioactivity were studied in albino and pigmented rats. The objectives of the study were to investigate differences in the disposition of chloroquine between albino and pigmented rats and to define its in‐vivo binding characteristics to melanin‐containing ocular tissues. Extensive uptake of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there was no quantitative differences in the distribution of radioactivity found between albino and pigmented rats except for melanin‐containing tissues, such as the uveal tract of the eye and perhaps hair follicles. There was selective and strong binding of drug‐related compounds to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value of 158.42 + 7.86 μg equiv g−1 (mean + s.e.) at 1 week and decreased very slowly with a terminal half life of 4476h (187 day). The uveal tract concentrations at 24 weeks were still high (67.75 + 6.19 μg equiv g−1). The AUC for uveal tract was 842.3 mg h g−1. A relatively high concentration was still determined in the uveal tract even at 48 weeks after single oral dosing by whole‐body autoradiography. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1 m HCl–EtOH (30:70) successively. In pigmented rats, almost all radioactivity was released from the tissue with 1 m HCl–EtOH (30:70), indicating that the strong binding by melanin was reversible, and that hydrophobic or electrostatic interaction would play a critical role in the binding of chloroquine and its metabolites with the melanin‐containing ocular tissues. Approximately 70% of the radioactivity given was recovered in urine and faeces up to 144h after dosing both in pigmented and albino rats. The excretion pattern in pigmented rats was similar to that seen in albino rats.</abstract><qualityIndicators><score>9.243</score><pdfWordCount>4243</pdfWordCount><pdfCharCount>25698</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>8</pdfPageCount><pdfPageSize>534.614 x 752.315 pts</pdfPageSize><pdfWordsPerPage>530</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>true</refBibsNative><abstractWordCount>334</abstractWordCount><abstractCharCount>2147</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Absorption, distribution and excretion of 14C‐chloroquine after single oral administration in albino and pigmented rats: binding characteristics of chloroquine‐related radioactivity to melanin in‐vivo</title><pmid><json:string>14738591</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>55</volume><issue>12</issue><pages><first>1647</first><last>1654</last><total>8</total></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>4476</json:string><json:string>2003</json:string></date><geogName></geogName><orgName><json:string>NJ</json:string><json:string>Leica Inc., Wetzlar, Germany</json:string><json:string>Aloka Co.</json:string><json:string>Packard Instrument Company</json:string><json:string>Brinkmann Co.</json:string><json:string>Beckman Coulter Inc.</json:string><json:string>Amersham Biosciences Corp.</json:string><json:string>Funabashi Farm Co.</json:string><json:string>Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co</json:string><json:string>Sankyo Labo Service Corporation Inc.</json:string><json:string>Japan Chiho Ono, Masayoshi Yamada, Makoto Tanaka Correspondence</json:string><json:string>Fuji Photo Film Co.</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>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>Salazar-Bookaman et al 1994</json:string><json:string>Larson & Tjalve 1979</json:string><json:string>Larsson 1993</json:string><json:string>Lindquist & Ullberg 1972</json:string><json:string>Ono & Tanaka 2003</json:string><json:string>È Stepien & Wilczok 1982</json:string><json:string>Kasuya et al 1976</json:string><json:string>Stepien & Wilczok 1982</json:string><json:string>Larsson & Tjalve 1979</json:string><json:string>Ono et al</json:string><json:string>Ings 1984</json:string><json:string>Jones 1999</json:string><json:string>SalazarBookaman et al 1994</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-4L384X5G-S</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>Chloroquine is an antimalarial agent that has been reported to have distinct affinity to melanin. After single oral administration of <hi rend="superscript">14</hi>C‐chloroquine at a dose of 20 mg kg<hi rend="superscript">−1</hi> under non‐fasting conditions, the absorption, distribution and excretion of <hi rend="superscript">14</hi>C‐chloroquine‐related radioactivity were studied in albino and pigmented rats. The objectives of the study were to investigate differences in the disposition of chloroquine between albino and pigmented rats and to define its in‐vivo binding characteristics to melanin‐containing ocular tissues. Extensive uptake of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there was no quantitative differences in the distribution of radioactivity found between albino and pigmented rats except for melanin‐containing tissues, such as the uveal tract of the eye and perhaps hair follicles. There was selective and strong binding of drug‐related compounds to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value of 158.42 + 7.86 μg equiv g<hi rend="superscript">−1</hi> (mean + s.e.) at 1 week and decreased very slowly with a terminal half life of 4476h (187 day). The uveal tract concentrations at 24 weeks were still high (67.75 + 6.19 μg equiv g<hi rend="superscript">−1</hi>). The AUC for uveal tract was 842.3 mg h g<hi rend="superscript">−1</hi>. A relatively high concentration was still determined in the uveal tract even at 48 weeks after single oral dosing by whole‐body autoradiography. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1 m HCl–EtOH (30:70) successively. In pigmented rats, almost all radioactivity was released from the tissue with 1 m HCl–EtOH (30:70), indicating that the strong binding by melanin was reversible, and that hydrophobic or electrostatic interaction would play a critical role in the binding of chloroquine and its metabolites with the melanin‐containing ocular tissues. Approximately 70% of the radioactivity given was recovered in urine and faeces up to 144h after dosing both in pigmented and albino rats. The excretion pattern in pigmented rats was similar to that seen in albino rats.</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-4L384X5G-S/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="12012"><doi origin="wiley">10.1111/jphp.2003.55.issue-12</doi><numberingGroup><numbering type="journalVolume" number="55">55</numbering><numbering type="journalIssue" number="12">12</numbering></numberingGroup><coverDate startDate="2003-12">December 2003</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="9" status="forIssue"><doi origin="wiley">10.1211/0022357022340</doi><idGroup><id type="unit" value="JPHP2471"></id></idGroup><countGroup><count type="pageTotal" number="8"></count></countGroup><titleGroup><title type="tocHeading1">Original Article</title></titleGroup><copyright>2003 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:2.3.6 mode:FullText source:HeaderRef result:HeaderRef" date="2010-04-21"></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="1647">1647</numbering><numbering type="pageLast" number="1654">1654</numbering></numberingGroup><correspondenceTo>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.JPHP2471.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received May 15, 2003; Accepted August 6, 2003</unparsedEditorialHistory><countGroup><count type="referenceTotal" number="11"></count><count type="linksCrossRef" number="4"></count></countGroup><titleGroup><title type="main">Absorption, distribution and excretion of <sup>14</sup>C‐chloroquine after single oral administration in albino and pigmented rats: binding characteristics of chloroquine‐related radioactivity to melanin in‐vivo</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>Chiho</givenNames><familyName>Ono</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>Masayoshi</givenNames><familyName>Yamada</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1" corresponding="yes"><personName><givenNames>Makoto</givenNames><familyName>Tanaka</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>Chloroquine is an antimalarial agent that has been reported to have distinct affinity to melanin. After single oral administration of <sup>14</sup>C‐chloroquine at a dose of 20 mg kg<sup>−1</sup> under non‐fasting conditions, the absorption, distribution and excretion of <sup>14</sup>C‐chloroquine‐related radioactivity were studied in albino and pigmented rats. The objectives of the study were to investigate differences in the disposition of chloroquine between albino and pigmented rats and to define its in‐vivo binding characteristics to melanin‐containing ocular tissues. Extensive uptake of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there was no quantitative differences in the distribution of radioactivity found between albino and pigmented rats except for melanin‐containing tissues, such as the uveal tract of the eye and perhaps hair follicles. There was selective and strong binding of drug‐related compounds to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value of 158.42 + 7.86 μg equiv g<sup>−1</sup> (mean + s.e.) at 1 week and decreased very slowly with a terminal half life of 4476h (187 day). The uveal tract concentrations at 24 weeks were still high (67.75 + 6.19 μg equiv g<sup>−1</sup>). The AUC for uveal tract was 842.3 mg h g<sup>−1</sup>. A relatively high concentration was still determined in the uveal tract even at 48 weeks after single oral dosing by whole‐body autoradiography. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1 m HCl–EtOH (30:70) successively. In pigmented rats, almost all radioactivity was released from the tissue with 1 m HCl–EtOH (30:70), indicating that the strong binding by melanin was reversible, and that hydrophobic or electrostatic interaction would play a critical role in the binding of chloroquine and its metabolites with the melanin‐containing ocular tissues. Approximately 70% of the radioactivity given was recovered in urine and faeces up to 144h after dosing both in pigmented and albino rats. The excretion pattern in pigmented rats was similar to that seen in albino rats.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Absorption, distribution and excretion of 14C‐chloroquine after single oral administration in albino and pigmented rats: binding characteristics of chloroquine‐related radioactivity to melanin in‐vivo</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Absorption, distribution and excretion of 14C‐chloroquine after single oral administration in albino and pigmented rats: binding characteristics of chloroquine‐related radioactivity to melanin in‐vivo</title></titleInfo><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><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><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">2003-12</dateIssued><edition>Received May 15, 2003; Accepted August 6, 2003</edition><copyrightDate encoding="w3cdtf">2003</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="references">11</extent><extent unit="linksCrossRef">4</extent></physicalDescription><abstract lang="en">Chloroquine is an antimalarial agent that has been reported to have distinct affinity to melanin. After single oral administration of 14C‐chloroquine at a dose of 20 mg kg−1 under non‐fasting conditions, the absorption, distribution and excretion of 14C‐chloroquine‐related radioactivity were studied in albino and pigmented rats. The objectives of the study were to investigate differences in the disposition of chloroquine between albino and pigmented rats and to define its in‐vivo binding characteristics to melanin‐containing ocular tissues. Extensive uptake of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there was no quantitative differences in the distribution of radioactivity found between albino and pigmented rats except for melanin‐containing tissues, such as the uveal tract of the eye and perhaps hair follicles. There was selective and strong binding of drug‐related compounds to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value of 158.42 + 7.86 μg equiv g−1 (mean + s.e.) at 1 week and decreased very slowly with a terminal half life of 4476h (187 day). The uveal tract concentrations at 24 weeks were still high (67.75 + 6.19 μg equiv g−1). The AUC for uveal tract was 842.3 mg h g−1. A relatively high concentration was still determined in the uveal tract even at 48 weeks after single oral dosing by whole‐body autoradiography. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1 m HCl–EtOH (30:70) successively. In pigmented rats, almost all radioactivity was released from the tissue with 1 m HCl–EtOH (30:70), indicating that the strong binding by melanin was reversible, and that hydrophobic or electrostatic interaction would play a critical role in the binding of chloroquine and its metabolites with the melanin‐containing ocular tissues. Approximately 70% of the radioactivity given was recovered in urine and faeces up to 144h after dosing both in pigmented and albino rats. 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