Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model
Identifieur interne : 000733 ( Istex/Corpus ); précédent : 000732; suivant : 000734Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model
Auteurs : J. M. Engasser ; F. Sarhan ; C. Falcoz ; M. Minier ; P. Letourneur ; G. SiestSource :
- Journal of Pharmaceutical Sciences [ 0022-3549 ] ; 1981-11.
English descriptors
- KwdEn :
- Alkyl, Aqueous sodium alkyl sulfonate, Barbituric, Barbituric acids, Bile, Bile rats, Biliary, Biliary excretion, Binding constants, Brain tissue, Concentration rebound, Different doses, Distribution volume, Dos, Drug binding, Drug concentration, Drug injection, Drug metab, Drug metabolism, Drug transport, Drug transport rate, Elimination kinetics, Elimination phase, Elimination rate, Enterohepatic, Enterohepatic cycle, Enterohepatic cycling, Excretion, First approximation, Free concentration, Free energy, Free liver tissue concentration, Free plasma concentration, High dose, Higher dose, Injection duration, Intestinal reabsorption, Intestinal resorption, Intravenous injection, Linear relationship, Liver metabolism, Metabolism, Microgram, Open symbols, Pharmaceutical sciences, Pharmacokinetic, Pharmacokinetic model, Phenobarbital, Phenobarbital distribution, Phenobarbital pharmacokinetics, Physiological models, Physiological parameters, Plasma binding, Plasma concentration, Plasma proteins, Present model, Publication march, Rebound, Residence time, Sodium alkyl sulfonate, Solid symbols, Solubilization, Solubilization process, Sulfonate, Theoretical curves, Thermodynamic functions, Total amount, Total blood concentration, Total plasma concentration, Total tissue concentration, Unchanged phenobarbital, Urinary, Urinary elimination, Urinary excretion, Various compartments, Various organs.
- Teeft :
- Alkyl, Aqueous sodium alkyl sulfonate, Barbituric, Barbituric acids, Bile, Bile rats, Biliary, Biliary excretion, Binding constants, Brain tissue, Concentration rebound, Different doses, Distribution volume, Dos, Drug binding, Drug concentration, Drug injection, Drug metab, Drug metabolism, Drug transport, Drug transport rate, Elimination kinetics, Elimination phase, Elimination rate, Enterohepatic, Enterohepatic cycle, Enterohepatic cycling, Excretion, First approximation, Free concentration, Free energy, Free liver tissue concentration, Free plasma concentration, High dose, Higher dose, Injection duration, Intestinal reabsorption, Intestinal resorption, Intravenous injection, Linear relationship, Liver metabolism, Metabolism, Microgram, Open symbols, Pharmaceutical sciences, Pharmacokinetic, Pharmacokinetic model, Phenobarbital, Phenobarbital distribution, Phenobarbital pharmacokinetics, Physiological models, Physiological parameters, Plasma binding, Plasma concentration, Plasma proteins, Present model, Publication march, Rebound, Residence time, Sodium alkyl sulfonate, Solid symbols, Solubilization, Solubilization process, Sulfonate, Theoretical curves, Thermodynamic functions, Total amount, Total blood concentration, Total plasma concentration, Total tissue concentration, Unchanged phenobarbital, Urinary, Urinary elimination, Urinary excretion, Various compartments, Various organs.
Abstract
The distribution, metabolism, and elimination kinetics at two different doses of phenobarbital were examined in rats. After intravenous injection, phenobarbital distributed very rapidly to the liver and kidneys, less rapidly to the muscle and gut, and much more slowly to the brain. At the higher dose, a concentration rebound was observed 1 hr after injection. In addition, phenobarbital distributed unevenly in various organs as a result of a different extent of drug binding. A physiologically based model, including enterohepatic cycling and diffusion resistances between blood and tissue, is proposed for phenobarbital pharmacokinetics. It satisfactorily describes phenobarbital distribution in rats at the two doses and allows an evaluation of fundamental physicobiochemical parameters such as drug‐tissue binding constants, blood‐tissue transport coefficients, metabolism, and elimination rate constants.
Url:
DOI: 10.1002/jps.2600701113
Links to Exploration step
ISTEX:4BBC7A180793359DFFE6C11057838897548126AELe document en format XML
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M." last="Engasser">J. M. Engasser</name><affiliation><mods:affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</mods:affiliation></affiliation></author><author><name sortKey="Sarhan, F" sort="Sarhan, F" uniqKey="Sarhan F" first="F." last="Sarhan">F. Sarhan</name><affiliation><mods:affiliation>Laboratoire de Biochimie Pharmacologique, Faculté de Pharmacie, 7, rue Albert Lebrun, 54001 Nancy, France</mods:affiliation></affiliation></author><author><name sortKey="Falcoz, C" sort="Falcoz, C" uniqKey="Falcoz C" first="C." last="Falcoz">C. 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dose</term><term>Injection duration</term><term>Intestinal reabsorption</term><term>Intestinal resorption</term><term>Intravenous injection</term><term>Linear relationship</term><term>Liver metabolism</term><term>Metabolism</term><term>Microgram</term><term>Open symbols</term><term>Pharmaceutical sciences</term><term>Pharmacokinetic</term><term>Pharmacokinetic model</term><term>Phenobarbital</term><term>Phenobarbital distribution</term><term>Phenobarbital pharmacokinetics</term><term>Physiological models</term><term>Physiological parameters</term><term>Plasma binding</term><term>Plasma concentration</term><term>Plasma proteins</term><term>Present model</term><term>Publication march</term><term>Rebound</term><term>Residence time</term><term>Sodium alkyl sulfonate</term><term>Solid symbols</term><term>Solubilization</term><term>Solubilization process</term><term>Sulfonate</term><term>Theoretical curves</term><term>Thermodynamic functions</term><term>Total amount</term><term>Total blood concentration</term><term>Total plasma concentration</term><term>Total tissue concentration</term><term>Unchanged phenobarbital</term><term>Urinary</term><term>Urinary elimination</term><term>Urinary excretion</term><term>Various compartments</term><term>Various organs</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Alkyl</term><term>Aqueous sodium alkyl sulfonate</term><term>Barbituric</term><term>Barbituric acids</term><term>Bile</term><term>Bile rats</term><term>Biliary</term><term>Biliary excretion</term><term>Binding constants</term><term>Brain tissue</term><term>Concentration rebound</term><term>Different doses</term><term>Distribution volume</term><term>Dos</term><term>Drug binding</term><term>Drug concentration</term><term>Drug injection</term><term>Drug metab</term><term>Drug metabolism</term><term>Drug transport</term><term>Drug transport rate</term><term>Elimination kinetics</term><term>Elimination phase</term><term>Elimination rate</term><term>Enterohepatic</term><term>Enterohepatic cycle</term><term>Enterohepatic cycling</term><term>Excretion</term><term>First approximation</term><term>Free concentration</term><term>Free energy</term><term>Free liver tissue concentration</term><term>Free plasma concentration</term><term>High dose</term><term>Higher dose</term><term>Injection duration</term><term>Intestinal reabsorption</term><term>Intestinal resorption</term><term>Intravenous injection</term><term>Linear relationship</term><term>Liver metabolism</term><term>Metabolism</term><term>Microgram</term><term>Open symbols</term><term>Pharmaceutical sciences</term><term>Pharmacokinetic</term><term>Pharmacokinetic model</term><term>Phenobarbital</term><term>Phenobarbital distribution</term><term>Phenobarbital pharmacokinetics</term><term>Physiological models</term><term>Physiological parameters</term><term>Plasma binding</term><term>Plasma concentration</term><term>Plasma proteins</term><term>Present model</term><term>Publication march</term><term>Rebound</term><term>Residence time</term><term>Sodium alkyl sulfonate</term><term>Solid symbols</term><term>Solubilization</term><term>Solubilization process</term><term>Sulfonate</term><term>Theoretical curves</term><term>Thermodynamic functions</term><term>Total amount</term><term>Total blood concentration</term><term>Total plasma concentration</term><term>Total tissue concentration</term><term>Unchanged phenobarbital</term><term>Urinary</term><term>Urinary elimination</term><term>Urinary excretion</term><term>Various compartments</term><term>Various organs</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The distribution, metabolism, and elimination kinetics at two different doses of phenobarbital were examined in rats. After intravenous injection, phenobarbital distributed very rapidly to the liver and kidneys, less rapidly to the muscle and gut, and much more slowly to the brain. At the higher dose, a concentration rebound was observed 1 hr after injection. In addition, phenobarbital distributed unevenly in various organs as a result of a different extent of drug binding. A physiologically based model, including enterohepatic cycling and diffusion resistances between blood and tissue, is proposed for phenobarbital pharmacokinetics. It satisfactorily describes phenobarbital distribution in rats at the two doses and allows an evaluation of fundamental physicobiochemical parameters such as drug‐tissue binding constants, blood‐tissue transport coefficients, metabolism, and elimination rate constants.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>phenobarbital</json:string><json:string>barbituric</json:string><json:string>microgram</json:string><json:string>barbituric acids</json:string><json:string>biliary</json:string><json:string>excretion</json:string><json:string>enterohepatic</json:string><json:string>biliary excretion</json:string><json:string>pharmacokinetic</json:string><json:string>distribution volume</json:string><json:string>solubilization</json:string><json:string>alkyl</json:string><json:string>concentration rebound</json:string><json:string>sulfonate</json:string><json:string>pharmaceutical sciences</json:string><json:string>phenobarbital distribution</json:string><json:string>enterohepatic cycle</json:string><json:string>urinary excretion</json:string><json:string>elimination phase</json:string><json:string>metabolism</json:string><json:string>dos</json:string><json:string>total plasma concentration</json:string><json:string>bile rats</json:string><json:string>free concentration</json:string><json:string>drug concentration</json:string><json:string>drug metab</json:string><json:string>drug binding</json:string><json:string>plasma concentration</json:string><json:string>plasma proteins</json:string><json:string>intravenous injection</json:string><json:string>drug injection</json:string><json:string>residence time</json:string><json:string>higher dose</json:string><json:string>sodium alkyl sulfonate</json:string><json:string>phenobarbital pharmacokinetics</json:string><json:string>linear relationship</json:string><json:string>pharmacokinetic model</json:string><json:string>solid symbols</json:string><json:string>aqueous sodium alkyl sulfonate</json:string><json:string>elimination rate</json:string><json:string>present model</json:string><json:string>open symbols</json:string><json:string>urinary</json:string><json:string>rebound</json:string><json:string>unchanged phenobarbital</json:string><json:string>drug metabolism</json:string><json:string>injection duration</json:string><json:string>total amount</json:string><json:string>total blood concentration</json:string><json:string>free plasma concentration</json:string><json:string>free energy</json:string><json:string>total tissue concentration</json:string><json:string>plasma binding</json:string><json:string>intestinal resorption</json:string><json:string>drug transport rate</json:string><json:string>various compartments</json:string><json:string>drug transport</json:string><json:string>urinary elimination</json:string><json:string>first approximation</json:string><json:string>theoretical curves</json:string><json:string>physiological parameters</json:string><json:string>liver metabolism</json:string><json:string>intestinal reabsorption</json:string><json:string>physiological models</json:string><json:string>brain tissue</json:string><json:string>binding constants</json:string><json:string>enterohepatic cycling</json:string><json:string>various organs</json:string><json:string>high dose</json:string><json:string>different doses</json:string><json:string>elimination kinetics</json:string><json:string>thermodynamic functions</json:string><json:string>publication march</json:string><json:string>solubilization process</json:string><json:string>free liver tissue concentration</json:string><json:string>bile</json:string></teeft></keywords><author><json:item><name>J. M. Engasser</name><affiliations><json:string>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</json:string><json:string>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</json:string></affiliations></json:item><json:item><name>F. Sarhan</name><affiliations><json:string>Laboratoire de Biochimie Pharmacologique, Faculté de Pharmacie, 7, rue Albert Lebrun, 54001 Nancy, France</json:string></affiliations></json:item><json:item><name>C. Falcoz</name><affiliations><json:string>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</json:string></affiliations></json:item><json:item><name>M. Minier</name><affiliations><json:string>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</json:string></affiliations></json:item><json:item><name>P. Letourneur</name><affiliations><json:string>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</json:string></affiliations></json:item><json:item><name>G. Siest</name><affiliations><json:string>Laboratoire de Biochimie Pharmacologique, Faculté de Pharmacie, 7, rue Albert Lebrun, 54001 Nancy, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Phenobarbital—physiologically based model for distribution, metabolism, and elimination kinetics in rats</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Models, pharmacokinetic—for phenobarbital distribution, metabolism, and elimination, rats</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Pharmacokinetics—model for phenobarbital distribution, metabolism, and elimination, rats</value></json:item></subject><articleId><json:string>JPS2600701113</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>The distribution, metabolism, and elimination kinetics at two different doses of phenobarbital were examined in rats. After intravenous injection, phenobarbital distributed very rapidly to the liver and kidneys, less rapidly to the muscle and gut, and much more slowly to the brain. At the higher dose, a concentration rebound was observed 1 hr after injection. In addition, phenobarbital distributed unevenly in various organs as a result of a different extent of drug binding. A physiologically based model, including enterohepatic cycling and diffusion resistances between blood and tissue, is proposed for phenobarbital pharmacokinetics. It satisfactorily describes phenobarbital distribution in rats at the two doses and allows an evaluation of fundamental physicobiochemical parameters such as drug‐tissue binding constants, blood‐tissue transport coefficients, metabolism, and elimination rate constants.</abstract><qualityIndicators><score>5.695</score><pdfVersion>1.3</pdfVersion><pdfPageSize>576 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>911</abstractCharCount><pdfWordCount>4207</pdfWordCount><pdfCharCount>26761</pdfCharCount><pdfPageCount>6</pdfPageCount><abstractWordCount>124</abstractWordCount></qualityIndicators><title>Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model</title><genre><json:string>article</json:string></genre><host><title>Journal of Pharmaceutical Sciences</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1520-6017</json:string></doi><issn><json:string>0022-3549</json:string></issn><eissn><json:string>1520-6017</json:string></eissn><publisherId><json:string>JPS</json:string></publisherId><volume>70</volume><issue>11</issue><pages><first>1233</first><last>1238</last><total>6</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Research Article</value></json:item></subject></host><categories><wos><json:string>science</json:string><json:string>pharmacology & pharmacy</json:string><json:string>chemistry, multidisciplinary</json:string><json:string>chemistry, medicinal</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>pharmacology & pharmacy</json:string></scienceMetrix><inist><json:string>sciences appliquees, technologies et medecines</json:string><json:string>sciences biologiques et medicales</json:string><json:string>sciences medicales</json:string></inist></categories><publicationDate>1981</publicationDate><copyrightDate>1981</copyrightDate><doi><json:string>10.1002/jps.2600701113</json:string></doi><id>4BBC7A180793359DFFE6C11057838897548126AE</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/4BBC7A180793359DFFE6C11057838897548126AE/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/4BBC7A180793359DFFE6C11057838897548126AE/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/4BBC7A180793359DFFE6C11057838897548126AE/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Washington</pubPlace><availability><licence>Copyright © 1981 Wiley‐Liss, Inc., A Wiley Company</licence></availability><date type="published" when="1981-11"></date></publicationStmt><notesStmt><note type="content-type" subtype="article" source="article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</note><note type="publication-type" subtype="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main" xml:lang="en">Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model</title><title level="a" type="short" xml:lang="en">Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model</title><author xml:id="author-0000" role="corresp"><persName><forename type="first">J. M.</forename><surname>Engasser</surname></persName><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France<address><country key="FR"></country></address></affiliation><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</affiliation></author><author xml:id="author-0001"><persName><forename type="first">F.</forename><surname>Sarhan</surname></persName><affiliation>Laboratoire de Biochimie Pharmacologique, Faculté de Pharmacie, 7, rue Albert Lebrun, 54001 Nancy, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">C.</forename><surname>Falcoz</surname></persName><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">M.</forename><surname>Minier</surname></persName><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">P.</forename><surname>Letourneur</surname></persName><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0005"><persName><forename type="first">G.</forename><surname>Siest</surname></persName><affiliation>Laboratoire de Biochimie Pharmacologique, Faculté de Pharmacie, 7, rue Albert Lebrun, 54001 Nancy, France<address><country key="FR"></country></address></affiliation></author><idno type="istex">4BBC7A180793359DFFE6C11057838897548126AE</idno><idno type="ark">ark:/67375/WNG-KDJ4FTRM-1</idno><idno type="DOI">10.1002/jps.2600701113</idno><idno type="unit">JPS2600701113</idno><idno type="toTypesetVersion">file:JPS.JPS2600701113.pdf</idno></analytic><monogr><title level="j" type="main">Journal of Pharmaceutical Sciences</title><title level="j" type="alt">JOURNAL OF PHARMACEUTICAL SCIENCES</title><idno type="pISSN">0022-3549</idno><idno type="eISSN">1520-6017</idno><idno type="book-DOI">10.1002/(ISSN)1520-6017</idno><idno type="book-part-DOI">10.1002/jps.v70:11</idno><idno type="product">JPS</idno><imprint><biblScope unit="vol">70</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1233">1233</biblScope><biblScope unit="page" to="1238">1238</biblScope><biblScope unit="page-count">6</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Washington</pubPlace><date type="published" when="1981-11"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>The distribution, metabolism, and elimination kinetics at two different doses of phenobarbital were examined in rats. After intravenous injection, phenobarbital distributed very rapidly to the liver and kidneys, less rapidly to the muscle and gut, and much more slowly to the brain. At the higher dose, a concentration rebound was observed 1 hr after injection. In addition, phenobarbital distributed unevenly in various organs as a result of a different extent of drug binding. A physiologically based model, including enterohepatic cycling and diffusion resistances between blood and tissue, is proposed for phenobarbital pharmacokinetics. 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After intravenous injection, phenobarbital distributed very rapidly to the liver and kidneys, less rapidly to the muscle and gut, and much more slowly to the brain. At the higher dose, a concentration rebound was observed 1 hr after injection. In addition, phenobarbital distributed unevenly in various organs as a result of a different extent of drug binding. A physiologically based model, including enterohepatic cycling and diffusion resistances between blood and tissue, is proposed for phenobarbital pharmacokinetics. It satisfactorily describes phenobarbital distribution in rats at the two doses and allows an evaluation of fundamental physicobiochemical parameters such as drug‐tissue binding constants, blood‐tissue transport coefficients, metabolism, and elimination rate constants.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Distribution, metabolism, and elimination of phenobarbital in rats: Physiologically based pharmacokinetic model</title></titleInfo><name type="personal"><namePart type="given">J. M.</namePart><namePart type="family">Engasser</namePart><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</affiliation><affiliation>Correspondence address: Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F.</namePart><namePart type="family">Sarhan</namePart><affiliation>Laboratoire de Biochimie Pharmacologique, Faculté de Pharmacie, 7, rue Albert Lebrun, 54001 Nancy, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Falcoz</namePart><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Minier</namePart><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Letourneur</namePart><affiliation>Laboratoire des Sciences du Génie Chimique, CNRS‐ENSIC, 1, rue Granduille, 54042 Nancy Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Siest</namePart><affiliation>Laboratoire de Biochimie Pharmacologique, Faculté de Pharmacie, 7, rue Albert Lebrun, 54001 Nancy, France</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>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Washington</placeTerm></place><dateIssued encoding="w3cdtf">1981-11</dateIssued><dateCaptured encoding="w3cdtf">1980-02-15</dateCaptured><dateValid encoding="w3cdtf">1981-03-26</dateValid><copyrightDate encoding="w3cdtf">1981</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">4</extent><extent unit="tables">1</extent><extent unit="references">30</extent></physicalDescription><abstract lang="en">The distribution, metabolism, and elimination kinetics at two different doses of phenobarbital were examined in rats. After intravenous injection, phenobarbital distributed very rapidly to the liver and kidneys, less rapidly to the muscle and gut, and much more slowly to the brain. At the higher dose, a concentration rebound was observed 1 hr after injection. In addition, phenobarbital distributed unevenly in various organs as a result of a different extent of drug binding. A physiologically based model, including enterohepatic cycling and diffusion resistances between blood and tissue, is proposed for phenobarbital pharmacokinetics. It satisfactorily describes phenobarbital distribution in rats at the two doses and allows an evaluation of fundamental physicobiochemical parameters such as drug‐tissue binding constants, blood‐tissue transport coefficients, metabolism, and elimination rate constants.</abstract><subject lang="en"><genre>keywords</genre><topic>Phenobarbital—physiologically based model for distribution, metabolism, and elimination kinetics in rats</topic><topic>Models, pharmacokinetic—for phenobarbital distribution, metabolism, and elimination, rats</topic><topic>Pharmacokinetics—model for phenobarbital distribution, metabolism, and elimination, rats</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Pharmaceutical Sciences</title></titleInfo><titleInfo type="abbreviated"><title>J. Pharm. 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