A Bodyweight-Dependent Allometric Exponent for Scaling Clearance Across the Human Life-Span
Identifieur interne : 000771 ( Main/Exploration ); précédent : 000770; suivant : 000772A Bodyweight-Dependent Allometric Exponent for Scaling Clearance Across the Human Life-Span
Auteurs : Chenguang Wang [Pays-Bas] ; Mariska Y. M. Peeters [Pays-Bas] ; Karel Allegaert [Belgique] ; Heleen J. Blussé Van Oud-Alblas [Pays-Bas] ; Elke H. J. Krekels [Pays-Bas] ; Dick Tibboel [Pays-Bas] ; Meindert Danhof [Pays-Bas] ; Catherijne A. J. Knibbe [Pays-Bas]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 2012.
Abstract
To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug.
Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using NONMEM VI. To scale clearance, a bodyweight-based exponential equation with four different structures for the exponent was used: (I) 3/4 allometric scaling model; (II) mixture model; (III) bodyweight-cut-point separated model; (IV) bodyweight-dependent exponent model.
Model I adequately described clearance in adults and older children, but overestimated clearance of neonates and underestimated clearance of infants. Use of two different exponents in Model II and Model III showed significantly improved performance, but yielded ambiguities on the boundaries of the two subpopulations. This discontinuity was overcome in Model IV, in which the exponent changed sigmoidally from 1.35 at a hypothetical bodyweight of 0 kg to a value of 0.56 from 10 kg onwards, thereby describing clearance of all individuals best.
A model was developed for scaling clearance over the entire human life-span with a single continuous equation, in which the exponent of the bodyweight-based exponential equation varied with bodyweight.
Url:
DOI: 10.1007/s11095-012-0668-x
PubMed: 22287046
PubMed Central: 3349030
Affiliations:
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J." last="Knibbe">Catherijne A. J. Knibbe</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Division of Pharmacology, LACDR, Leiden University, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3">Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein</wicri:regionArea><wicri:noRegion>3430 EM Nieuwegein</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22287046</idno><idno type="pmc">3349030</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349030</idno><idno type="RBID">PMC:3349030</idno><idno type="doi">10.1007/s11095-012-0668-x</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000171</idno><idno type="wicri:Area/Pmc/Curation">000171</idno><idno type="wicri:Area/Pmc/Checkpoint">000332</idno><idno type="wicri:Area/Ncbi/Merge">000122</idno><idno type="wicri:Area/Ncbi/Curation">000122</idno><idno type="wicri:Area/Ncbi/Checkpoint">000122</idno><idno type="wicri:doubleKey">0724-8741:2012:Wang C:a:bodyweight:dependent</idno><idno type="wicri:Area/Main/Merge">000772</idno><idno type="wicri:Area/Main/Curation">000771</idno><idno type="wicri:Area/Main/Exploration">000771</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Bodyweight-Dependent Allometric Exponent for Scaling Clearance Across the Human Life-Span</title><author><name sortKey="Wang, Chenguang" sort="Wang, Chenguang" uniqKey="Wang C" first="Chenguang" last="Wang">Chenguang Wang</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Division of Pharmacology, LACDR, Leiden University, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Peeters, Mariska Y M" sort="Peeters, Mariska Y M" uniqKey="Peeters M" first="Mariska Y. M." last="Peeters">Mariska Y. M. Peeters</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein</wicri:regionArea><wicri:noRegion>3430 EM Nieuwegein</wicri:noRegion></affiliation></author><author><name sortKey="Allegaert, Karel" sort="Allegaert, Karel" uniqKey="Allegaert K" first="Karel" last="Allegaert">Karel Allegaert</name><affiliation wicri:level="1"><nlm:aff id="Aff4">Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Blusse Van Oud Alblas, Heleen J" sort="Blusse Van Oud Alblas, Heleen J" uniqKey="Blusse Van Oud Alblas H" first="Heleen J." last="Blussé Van Oud-Alblas">Heleen J. Blussé Van Oud-Alblas</name><affiliation wicri:level="3"><nlm:aff id="Aff5">Department of Anesthesiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Anesthesiology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Krekels, Elke H J" sort="Krekels, Elke H J" uniqKey="Krekels E" first="Elke H. J." last="Krekels">Elke H. J. Krekels</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Division of Pharmacology, LACDR, Leiden University, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Tibboel, Dick" sort="Tibboel, Dick" uniqKey="Tibboel D" first="Dick" last="Tibboel">Dick Tibboel</name><affiliation wicri:level="3"><nlm:aff id="Aff2">Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Danhof, Meindert" sort="Danhof, Meindert" uniqKey="Danhof M" first="Meindert" last="Danhof">Meindert Danhof</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Division of Pharmacology, LACDR, Leiden University, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Knibbe, Catherijne A J" sort="Knibbe, Catherijne A J" uniqKey="Knibbe C" first="Catherijne A. J." last="Knibbe">Catherijne A. J. Knibbe</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Division of Pharmacology, LACDR, Leiden University, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3">Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein</wicri:regionArea><wicri:noRegion>3430 EM Nieuwegein</wicri:noRegion></affiliation></author></analytic><series><title level="j">Pharmaceutical Research</title><idno type="ISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><sec><title>Purpose</title><p>To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug.</p></sec><sec><title>Methods</title><p>Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using NONMEM VI. To scale clearance, a bodyweight-based exponential equation with four different structures for the exponent was used: (I) 3/4 allometric scaling model; (II) mixture model; (III) bodyweight-cut-point separated model; (IV) bodyweight-dependent exponent model.</p></sec><sec><title>Results</title><p>Model I adequately described clearance in adults and older children, but overestimated clearance of neonates and underestimated clearance of infants. Use of two different exponents in Model II and Model III showed significantly improved performance, but yielded ambiguities on the boundaries of the two subpopulations. This discontinuity was overcome in Model IV, in which the exponent changed sigmoidally from 1.35 at a hypothetical bodyweight of 0 kg to a value of 0.56 from 10 kg onwards, thereby describing clearance of all individuals best.</p></sec><sec><title>Conclusions</title><p>A model was developed for scaling clearance over the entire human life-span with a single continuous equation, in which the exponent of the bodyweight-based exponential equation varied with bodyweight.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Anderson, Bj" uniqKey="Anderson B">BJ Anderson</name></author><author><name sortKey="Holford, Nh" uniqKey="Holford N">NH Holford</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kleiber, M" uniqKey="Kleiber M">M Kleiber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="West, Gb" uniqKey="West G">GB West</name></author><author><name sortKey="Brown, 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uniqKey="Alcorn J">J Alcorn</name></author><author><name sortKey="Mcnamara, Pj" uniqKey="Mcnamara P">PJ McNamara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Strassburg, Cp" uniqKey="Strassburg C">CP Strassburg</name></author><author><name sortKey="Strassburg, A" uniqKey="Strassburg A">A Strassburg</name></author><author><name sortKey="Kneip, S" uniqKey="Kneip S">S Kneip</name></author><author><name sortKey="Barut, A" uniqKey="Barut A">A Barut</name></author><author><name sortKey="Tukey, Rh" uniqKey="Tukey R">RH Tukey</name></author><author><name sortKey="Rodeck, B" uniqKey="Rodeck B">B Rodeck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Allegaert, K" uniqKey="Allegaert K">K Allegaert</name></author><author><name sortKey="Rayyan, M" uniqKey="Rayyan M">M Rayyan</name></author><author><name sortKey="Hoon, J" uniqKey="Hoon J">J Hoon</name></author><author><name sortKey="Tibboel, D" uniqKey="Tibboel D">D Tibboel</name></author><author><name sortKey="Verbesselt, R" uniqKey="Verbesselt R">R Verbesselt</name></author><author><name sortKey="Naulaers, G" uniqKey="Naulaers G">G Naulaers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holford, Nh" uniqKey="Holford N">NH Holford</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Tn" uniqKey="Johnson T">TN Johnson</name></author><author><name sortKey="Rostami Hodjegan, A" uniqKey="Rostami Hodjegan A">A Rostami-Hodjegan</name></author><author><name sortKey="Tucker, Gt" uniqKey="Tucker G">GT Tucker</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Belgique</li><li>Pays-Bas</li></country><region><li>Hollande-Méridionale</li></region><settlement><li>Leyde</li><li>Rotterdam</li></settlement></list><tree><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Wang, Chenguang" sort="Wang, Chenguang" uniqKey="Wang C" first="Chenguang" last="Wang">Chenguang Wang</name></region><name sortKey="Blusse Van Oud Alblas, Heleen J" sort="Blusse Van Oud Alblas, Heleen J" uniqKey="Blusse Van Oud Alblas H" first="Heleen J." last="Blussé Van Oud-Alblas">Heleen J. Blussé Van Oud-Alblas</name><name sortKey="Danhof, Meindert" sort="Danhof, Meindert" uniqKey="Danhof M" first="Meindert" last="Danhof">Meindert Danhof</name><name sortKey="Knibbe, Catherijne A J" sort="Knibbe, Catherijne A J" uniqKey="Knibbe C" first="Catherijne A. J." last="Knibbe">Catherijne A. J. Knibbe</name><name sortKey="Knibbe, Catherijne A J" sort="Knibbe, Catherijne A J" uniqKey="Knibbe C" first="Catherijne A. J." last="Knibbe">Catherijne A. J. Knibbe</name><name sortKey="Knibbe, Catherijne A J" sort="Knibbe, Catherijne A J" uniqKey="Knibbe C" first="Catherijne A. J." last="Knibbe">Catherijne A. J. Knibbe</name><name sortKey="Krekels, Elke H J" sort="Krekels, Elke H J" uniqKey="Krekels E" first="Elke H. J." last="Krekels">Elke H. J. Krekels</name><name sortKey="Krekels, Elke H J" sort="Krekels, Elke H J" uniqKey="Krekels E" first="Elke H. J." last="Krekels">Elke H. J. Krekels</name><name sortKey="Peeters, Mariska Y M" sort="Peeters, Mariska Y M" uniqKey="Peeters M" first="Mariska Y. M." last="Peeters">Mariska Y. M. Peeters</name><name sortKey="Tibboel, Dick" sort="Tibboel, Dick" uniqKey="Tibboel D" first="Dick" last="Tibboel">Dick Tibboel</name><name sortKey="Wang, Chenguang" sort="Wang, Chenguang" uniqKey="Wang C" first="Chenguang" last="Wang">Chenguang Wang</name></country><country name="Belgique"><noRegion><name sortKey="Allegaert, Karel" sort="Allegaert, Karel" uniqKey="Allegaert K" first="Karel" last="Allegaert">Karel Allegaert</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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