The role of population PK–PD modelling in paediatric clinical research
Identifieur interne : 000201 ( Pmc/Curation ); précédent : 000200; suivant : 000202The role of population PK–PD modelling in paediatric clinical research
Auteurs : Roosmarijn F. W. De Cock [Pays-Bas] ; Chiara Piana [Pays-Bas] ; Elke H. J. Krekels [Pays-Bas] ; Meindert Danhof [Pays-Bas] ; Karel Allegaert [Belgique] ; Catherijne A. J. Knibbe [Pays-Bas]Source :
- European Journal of Clinical Pharmacology [ 0031-6970 ] ; 2010.
Abstract
Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK–PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK–PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK–PD parameters with the highest precision. Once a population PK–PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child.
Url:
DOI: 10.1007/s00228-009-0782-9
PubMed: 20340012
PubMed Central: 3082690
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000201
Links to Exploration step
PMC:3082690Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The role of population PK–PD modelling in paediatric clinical research</title>
<author><name sortKey="De Cock, Roosmarijn F W" sort="De Cock, Roosmarijn F W" uniqKey="De Cock R" first="Roosmarijn F. W." last="De Cock">Roosmarijn F. W. De Cock</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Piana, Chiara" sort="Piana, Chiara" uniqKey="Piana C" first="Chiara" last="Piana">Chiara Piana</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</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="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Danhof, Meindert" sort="Danhof, Meindert" uniqKey="Danhof M" first="Meindert" last="Danhof">Meindert Danhof</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</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 Hospital Leuven, Leuven, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Neonatal Intensive Care Unit, University Hospital Leuven, Leuven</wicri:regionArea>
</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="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam</wicri:regionArea>
</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">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">20340012</idno>
<idno type="pmc">3082690</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082690</idno>
<idno type="RBID">PMC:3082690</idno>
<idno type="doi">10.1007/s00228-009-0782-9</idno>
<date when="2010">2010</date>
<idno type="wicri:Area/Pmc/Corpus">000201</idno>
<idno type="wicri:Area/Pmc/Curation">000201</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The role of population PK–PD modelling in paediatric clinical research</title>
<author><name sortKey="De Cock, Roosmarijn F W" sort="De Cock, Roosmarijn F W" uniqKey="De Cock R" first="Roosmarijn F. W." last="De Cock">Roosmarijn F. W. De Cock</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Piana, Chiara" sort="Piana, Chiara" uniqKey="Piana C" first="Chiara" last="Piana">Chiara Piana</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</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="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Danhof, Meindert" sort="Danhof, Meindert" uniqKey="Danhof M" first="Meindert" last="Danhof">Meindert Danhof</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</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 Hospital Leuven, Leuven, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Neonatal Intensive Care Unit, University Hospital Leuven, Leuven</wicri:regionArea>
</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="1"><nlm:aff id="Aff1">Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam</wicri:regionArea>
</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">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">European Journal of Clinical Pharmacology</title>
<idno type="ISSN">0031-6970</idno>
<idno type="eISSN">1432-1041</idno>
<imprint><date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK–PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK–PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK–PD parameters with the highest precision. Once a population PK–PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ernest, Tb" uniqKey="Ernest T">TB Ernest</name>
</author>
<author><name sortKey="Elder, Dp" uniqKey="Elder D">DP Elder</name>
</author>
<author><name sortKey="Martini, Lg" uniqKey="Martini L">LG Martini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jong, Gw" uniqKey="Jong G">GW Jong</name>
</author>
<author><name sortKey="Vulto, Ag" uniqKey="Vulto A">AG Vulto</name>
</author>
<author><name sortKey="Hoog, M" uniqKey="Hoog M">M Hoog</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Conroy, S" uniqKey="Conroy S">S Conroy</name>
</author>
<author><name sortKey="Choonara, I" uniqKey="Choonara I">I Choonara</name>
</author>
<author><name sortKey="Impicciatore, P" uniqKey="Impicciatore P">P Impicciatore</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tod, M" uniqKey="Tod M">M Tod</name>
</author>
<author><name sortKey="Jullien, V" uniqKey="Jullien V">V Jullien</name>
</author>
<author><name sortKey="Pons, G" uniqKey="Pons G">G Pons</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bray, Rj" uniqKey="Bray R">RJ Bray</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Parke, Tj" uniqKey="Parke T">TJ Parke</name>
</author>
<author><name sortKey="Stevens, Je" uniqKey="Stevens J">JE Stevens</name>
</author>
<author><name sortKey="Rice, As" uniqKey="Rice A">AS Rice</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sutherland, Jm" uniqKey="Sutherland J">JM Sutherland</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mcintyre, J" uniqKey="Mcintyre J">J McIntyre</name>
</author>
<author><name sortKey="Choonara, I" uniqKey="Choonara I">I Choonara</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Dunne, J" uniqKey="Dunne J">J Dunne</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Saint Raymond, A" uniqKey="Saint Raymond A">A Saint Raymond</name>
</author>
<author><name sortKey="Brasseur, D" uniqKey="Brasseur D">D Brasseur</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kearns, Gl" uniqKey="Kearns G">GL Kearns</name>
</author>
<author><name sortKey="Abdel Rahman, Sm" uniqKey="Abdel Rahman S">SM Abdel-Rahman</name>
</author>
<author><name sortKey="Alander, Sw" uniqKey="Alander S">SW Alander</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Grand, Rj" uniqKey="Grand R">RJ Grand</name>
</author>
<author><name sortKey="Watkins, Jb" uniqKey="Watkins J">JB Watkins</name>
</author>
<author><name sortKey="Torti, Fm" uniqKey="Torti F">FM Torti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anderson, Bj" uniqKey="Anderson B">BJ Anderson</name>
</author>
<author><name sortKey="Lingen, Ra" uniqKey="Lingen R">RA Lingen</name>
</author>
<author><name sortKey="Hansen, Tg" uniqKey="Hansen T">TG Hansen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hines, Rn" uniqKey="Hines R">RN Hines</name>
</author>
<author><name sortKey="Mccarver, Dg" uniqKey="Mccarver D">DG McCarver</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wildt, Sn" uniqKey="Wildt S">SN Wildt</name>
</author>
<author><name sortKey="Kearns, Gl" uniqKey="Kearns G">GL Kearns</name>
</author>
<author><name sortKey="Leeder, Js" uniqKey="Leeder J">JS Leeder</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Leeder, Js" uniqKey="Leeder J">JS Leeder</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Krekels, Eh" uniqKey="Krekels E">EH Krekels</name>
</author>
<author><name sortKey="Anker, Jn" uniqKey="Anker J">JN Anker</name>
</author>
<author><name sortKey="Baiardi, P" uniqKey="Baiardi P">P Baiardi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rhodin, Mm" uniqKey="Rhodin M">MM Rhodin</name>
</author>
<author><name sortKey="Anderson, Bj" uniqKey="Anderson B">BJ Anderson</name>
</author>
<author><name sortKey="Peters, Am" uniqKey="Peters A">AM Peters</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bartelink, Ih" uniqKey="Bartelink I">IH Bartelink</name>
</author>
<author><name sortKey="Rademaker, Cm" uniqKey="Rademaker C">CM Rademaker</name>
</author>
<author><name sortKey="Schobben, Af" uniqKey="Schobben A">AF Schobben</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Knibbe, Ca" uniqKey="Knibbe C">CA Knibbe</name>
</author>
<author><name sortKey="Koster, Vs" uniqKey="Koster V">VS Koster</name>
</author>
<author><name sortKey="Deneer, Vh" uniqKey="Deneer V">VH Deneer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rauh, M" uniqKey="Rauh M">M Rauh</name>
</author>
<author><name sortKey="Stachel, D" uniqKey="Stachel D">D Stachel</name>
</author>
<author><name sortKey="Kuhlen, M" uniqKey="Kuhlen M">M Kuhlen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Edelbroek, Pm" uniqKey="Edelbroek P">PM Edelbroek</name>
</author>
<author><name sortKey="Heijden, J" uniqKey="Heijden J">J Heijden</name>
</author>
<author><name sortKey="Stolk, Lm" uniqKey="Stolk L">LM Stolk</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jabeen, R" uniqKey="Jabeen R">R Jabeen</name>
</author>
<author><name sortKey="Payne, D" uniqKey="Payne D">D Payne</name>
</author>
<author><name sortKey="Wiktorowicz, J" uniqKey="Wiktorowicz J">J Wiktorowicz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fisher, Dm" uniqKey="Fisher D">DM Fisher</name>
</author>
<author><name sortKey="O Eeffe, C" uniqKey="O Eeffe C">C O’Keeffe</name>
</author>
<author><name sortKey="Stanski, Dr" uniqKey="Stanski D">DR Stanski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ledez, Km" uniqKey="Ledez K">KM LeDez</name>
</author>
<author><name sortKey="Lerman, J" uniqKey="Lerman J">J Lerman</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Stephenson, T" uniqKey="Stephenson T">T Stephenson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dijk, M" uniqKey="Dijk M">M Dijk</name>
</author>
<author><name sortKey="Boer, Jb" uniqKey="Boer J">JB Boer</name>
</author>
<author><name sortKey="Koot, Hm" uniqKey="Koot H">HM Koot</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Peeters, My" uniqKey="Peeters M">MY Peeters</name>
</author>
<author><name sortKey="Prins, Sa" uniqKey="Prins S">SA Prins</name>
</author>
<author><name sortKey="Knibbe, Ca" uniqKey="Knibbe C">CA Knibbe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Peeters, My" uniqKey="Peeters M">MY Peeters</name>
</author>
<author><name sortKey="Prins, Sa" uniqKey="Prins S">SA Prins</name>
</author>
<author><name sortKey="Knibbe, Ca" uniqKey="Knibbe C">CA Knibbe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dijk, M" uniqKey="Dijk M">M Dijk</name>
</author>
<author><name sortKey="Peters, Jw" uniqKey="Peters J">JW Peters</name>
</author>
<author><name sortKey="Deventer, P" uniqKey="Deventer P">P Deventer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jonsson, En" uniqKey="Jonsson E">EN Jonsson</name>
</author>
<author><name sortKey="Karlsson, Mo" uniqKey="Karlsson M">MO Karlsson</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Beal, Sl" uniqKey="Beal S">SL Beal</name>
</author>
<author><name sortKey="Sheiner, Lb" uniqKey="Sheiner L">LB Sheiner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ette, Ei" uniqKey="Ette E">EI Ette</name>
</author>
<author><name sortKey="Williams, Pj" uniqKey="Williams P">PJ Williams</name>
</author>
<author><name sortKey="Lane, Jr" uniqKey="Lane J">JR Lane</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wade, Jr" uniqKey="Wade J">JR Wade</name>
</author>
<author><name sortKey="Beal, Sl" uniqKey="Beal S">SL Beal</name>
</author>
<author><name sortKey="Sambol, Nc" uniqKey="Sambol N">NC Sambol</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aarons, L" uniqKey="Aarons L">L Aarons</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Beal, Sl" uniqKey="Beal S">SL Beal</name>
</author>
<author><name sortKey="Broeckman, Aj" uniqKey="Broeckman A">AJ Broeckman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sl, Beal" uniqKey="Sl B">Beal SL</name>
</author>
<author><name sortKey="Broeckman, Aj" uniqKey="Broeckman A">AJ Broeckman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jelliffe, Rsa" uniqKey="Jelliffe R">RSA Jelliffe</name>
</author>
<author><name sortKey="Guilder, M" uniqKey="Guilder M">M Guilder</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bustad, A" uniqKey="Bustad A">A Bustad</name>
</author>
<author><name sortKey="Terziivanov, D" uniqKey="Terziivanov D">D Terziivanov</name>
</author>
<author><name sortKey="Leary, R" uniqKey="Leary R">R Leary</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mentre, F" uniqKey="Mentre F">F Mentre</name>
</author>
<author><name sortKey="Mallet, A" uniqKey="Mallet A">A Mallet</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mandema, Jw" uniqKey="Mandema J">JW Mandema</name>
</author>
<author><name sortKey="Verotta, D" uniqKey="Verotta D">D Verotta</name>
</author>
<author><name sortKey="Sheiner, Lb" uniqKey="Sheiner L">LB Sheiner</name>
</author>
</analytic>
</biblStruct>
<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="Anderson, Bj" uniqKey="Anderson B">BJ Anderson</name>
</author>
<author><name sortKey="Allegaert, K" uniqKey="Allegaert K">K Allegaert</name>
</author>
<author><name sortKey="Holford, Nh" uniqKey="Holford N">NH Holford</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anderson, Bj" uniqKey="Anderson B">BJ Anderson</name>
</author>
<author><name sortKey="Allegaert, K" uniqKey="Allegaert K">K Allegaert</name>
</author>
<author><name sortKey="Holford, Nh" uniqKey="Holford N">NH Holford</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meibohm, B" uniqKey="Meibohm B">B Meibohm</name>
</author>
<author><name sortKey="Laer, S" uniqKey="Laer S">S Laer</name>
</author>
<author><name sortKey="Panetta, Jc" uniqKey="Panetta J">JC Panetta</name>
</author>
</analytic>
</biblStruct>
<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="Engle, Wa" uniqKey="Engle W">WA Engle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Allegaert, K" uniqKey="Allegaert K">K Allegaert</name>
</author>
<author><name sortKey="Anderson, Bj" uniqKey="Anderson B">BJ Anderson</name>
</author>
<author><name sortKey="Cossey, V" uniqKey="Cossey V">V Cossey</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Knibbe, Ca" uniqKey="Knibbe C">CA Knibbe</name>
</author>
<author><name sortKey="Krekels, Eh" uniqKey="Krekels E">EH Krekels</name>
</author>
<author><name sortKey="Anker, Jn" uniqKey="Anker J">JN Anker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mahmood, I" uniqKey="Mahmood I">I Mahmood</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mahmood, I" uniqKey="Mahmood I">I Mahmood</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sheiner, Lb" uniqKey="Sheiner L">LB Sheiner</name>
</author>
<author><name sortKey="Ludden, Tm" uniqKey="Ludden T">TM Ludden</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Karlsson, Mo" uniqKey="Karlsson M">MO Karlsson</name>
</author>
<author><name sortKey="Savic, Rm" uniqKey="Savic R">RM Savic</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Box, G" uniqKey="Box G">G Box</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brendel, K" uniqKey="Brendel K">K Brendel</name>
</author>
<author><name sortKey="Dartois, C" uniqKey="Dartois C">C Dartois</name>
</author>
<author><name sortKey="Comets, E" uniqKey="Comets E">E Comets</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ince, I" uniqKey="Ince I">I Ince</name>
</author>
<author><name sortKey="Wildt, Sn" uniqKey="Wildt S">SN Wildt</name>
</author>
<author><name sortKey="Tibboel, D" uniqKey="Tibboel D">D Tibboel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hooker, Ac" uniqKey="Hooker A">AC Hooker</name>
</author>
<author><name sortKey="Staatz, Ce" uniqKey="Staatz C">CE Staatz</name>
</author>
<author><name sortKey="Karlsson, Mo" uniqKey="Karlsson M">MO Karlsson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fang, L" uniqKey="Fang L">L Fang</name>
</author>
<author><name sortKey="Holford, Nh" uniqKey="Holford N">NH Holford</name>
</author>
<author><name sortKey="Hinkle, G" uniqKey="Hinkle G">G Hinkle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brendel, K" uniqKey="Brendel K">K Brendel</name>
</author>
<author><name sortKey="Comets, E" uniqKey="Comets E">E Comets</name>
</author>
<author><name sortKey="Laffont, C" uniqKey="Laffont C">C Laffont</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Comets, E" uniqKey="Comets E">E Comets</name>
</author>
<author><name sortKey="Brendel, K" uniqKey="Brendel K">K Brendel</name>
</author>
<author><name sortKey="Mentre, F" uniqKey="Mentre F">F Mentre</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Foracchia, M" uniqKey="Foracchia M">M Foracchia</name>
</author>
<author><name sortKey="Hooker, A" uniqKey="Hooker A">A Hooker</name>
</author>
<author><name sortKey="Vicini, P" uniqKey="Vicini P">P Vicini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Duffull, Sb" uniqKey="Duffull S">SB Duffull</name>
</author>
<author><name sortKey="Eccleston, J" uniqKey="Eccleston J">J Eccleston</name>
</author>
<author><name sortKey="Kimco, H" uniqKey="Kimco H">H Kimco</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Retout, S" uniqKey="Retout S">S Retout</name>
</author>
<author><name sortKey="Mentre, F" uniqKey="Mentre F">F Mentre</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Duffull, Sb" uniqKey="Duffull S">SB Duffull</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Knibbe, Ca" uniqKey="Knibbe C">CA Knibbe</name>
</author>
<author><name sortKey="Melenhorst De Jong, G" uniqKey="Melenhorst De Jong G">G Melenhorst-de Jong</name>
</author>
<author><name sortKey="Mestrom, M" uniqKey="Mestrom M">M Mestrom</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Breimer, Dd" uniqKey="Breimer D">DD Breimer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Alcorn, J" 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="Johnson, Tn" uniqKey="Johnson T">TN Johnson</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Eur J Clin Pharmacol</journal-id>
<journal-title-group><journal-title>European Journal of Clinical Pharmacology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0031-6970</issn>
<issn pub-type="epub">1432-1041</issn>
<publisher><publisher-name>Springer-Verlag</publisher-name>
<publisher-loc>Berlin/Heidelberg</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20340012</article-id>
<article-id pub-id-type="pmc">3082690</article-id>
<article-id pub-id-type="publisher-id">782</article-id>
<article-id pub-id-type="doi">10.1007/s00228-009-0782-9</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>The role of population PK–PD modelling in paediatric clinical research</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>De Cock</surname>
<given-names>Roosmarijn F. W.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Piana</surname>
<given-names>Chiara</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Krekels</surname>
<given-names>Elke H. J.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Danhof</surname>
<given-names>Meindert</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Allegaert</surname>
<given-names>Karel</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Knibbe</surname>
<given-names>Catherijne A. J.</given-names>
</name>
<address><email>c.knibbe@antoniusziekenhuis.nl</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<aff id="Aff1"><label>1</label>
Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands</aff>
<aff id="Aff2"><label>2</label>
Department of Pediatric Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands</aff>
<aff id="Aff3"><label>3</label>
Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, The Netherlands</aff>
<aff id="Aff4"><label>4</label>
Neonatal Intensive Care Unit, University Hospital Leuven, Leuven, Belgium</aff>
</contrib-group>
<pub-date pub-type="epub"><day>26</day>
<month>3</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>26</day>
<month>3</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="ppub"><month>5</month>
<year>2011</year>
</pub-date>
<volume>67</volume>
<issue>Suppl 1</issue>
<fpage>5</fpage>
<lpage>16</lpage>
<history><date date-type="received"><day>9</day>
<month>7</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>22</day>
<month>12</month>
<year>2009</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s) 2010</copyright-statement>
</permissions>
<abstract id="Abs1"><p>Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK–PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK–PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK–PD parameters with the highest precision. Once a population PK–PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child.</p>
</abstract>
<kwd-group><title>Keywords</title>
<kwd>Pharmacokinetics</kwd>
<kwd>Pharmacodynamics</kwd>
<kwd>Population modelling</kwd>
<kwd>Paediatric population</kwd>
<kwd>Validation</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© Springer-Verlag 2011</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Belgique/explor/OpenAccessBelV2/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000201 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000201 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Belgique |area= OpenAccessBelV2 |flux= Pmc |étape= Curation |type= RBID |clé= PMC:3082690 |texte= The role of population PK–PD modelling in paediatric clinical research }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:20340012" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \ | NlmPubMed2Wicri -a OpenAccessBelV2
![]() | This area was generated with Dilib version V0.6.25. | ![]() |