Pediatric Physiologically Based Pharmacokinetic Model Development: Current Status and Challenges View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-12

AUTHORS

Wen Lin, Jing-He Yan, Tycho Heimbach, Handan He

ABSTRACT

This article provides a brief overview of the development of pediatric physiologically based pharmacokinetic (PPBPK) models, the challenges of uncertain systems information, and finally performance verification considering recent regulatory guidance. Pediatric PBPK (PPBPK) model can incorporate varied manifolds of drug and developmental system information to predict drug PK in children. Health authorities have been receiving a growing number of drug submissions that have used PPBPK. According to a recent review of the FDA office of Clinical Pharmacology, PPBPK modeling has been readily applied for dose regimen selection in a variety of pediatric patient groups via a “learn and confirm” approach. Before applying to pediatrics, a PBPK model is developed using physicochemical, biopharmaceutical, and metabolic parameters of drug and then verified by pharmacokinetics (PK) data in adults. Once the drug parameters are optimized, they can be used in the PPBPK model which contains the ‘systemic’ data of physiology and biochemistry in children. The drug absorption, distribution, metabolism, and excretion (ADME) parameters can be estimated according to developmental changes in physiology and biochemistry in various age groups of children. The model is then applied to simulate the exposure in children. The current challenge is the paucity of available pediatric systems information and oral biopharmaceutics. They are essential to verify PPBPK models and predict PK particularly in neonates and young infants. The recent research on intestinal and hepatic transporter ontogeny, via mRNA and proteomic data, gives us increased understanding of pediatric drug absorption, hepatic uptake, and biliary excretion. Nevertheless, more validated developmental ‘system’ data is needed in this field. Another gap is the lack of good quality pediatric drug studies performed across the age range, which currently is a limitation to the performance verification of PPBPK models. PPBPK models have already improved the pediatric drug development process but the important challenges lie ahead. Further development and verification are constantly required. It may be possible to minimize the number of pediatric subjects used in PK studies and avoid some studies altogether. More... »

PAGES

1-11

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s40495-018-0162-1

DOI

http://dx.doi.org/10.1007/s40495-018-0162-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110345002


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1115", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Pharmacology and Pharmaceutical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "PK Sciences, Novartis Institutes for Biomedical Research, 07936, East Hanover, NJ, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lin", 
        "givenName": "Wen", 
        "id": "sg:person.01063055771.51", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01063055771.51"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "PK Sciences, Novartis Institutes for Biomedical Research, 07936, East Hanover, NJ, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yan", 
        "givenName": "Jing-He", 
        "id": "sg:person.0747467571.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0747467571.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "PK Sciences, Novartis Institutes for Biomedical Research, 07936, East Hanover, NJ, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Heimbach", 
        "givenName": "Tycho", 
        "id": "sg:person.01012730002.36", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01012730002.36"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "PK Sciences, Novartis Institutes for Biomedical Research, 07936, East Hanover, NJ, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "He", 
        "givenName": "Handan", 
        "id": "sg:person.0673341315.60", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0673341315.60"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1007/s11095-015-1762-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003501773", 
          "https://doi.org/10.1007/s11095-015-1762-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/clpt.2012.68", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004025588", 
          "https://doi.org/10.1038/clpt.2012.68"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.116.069559", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004594547"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1460-9592.2011.03782.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005207943"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/pr.2015.119", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005211732", 
          "https://doi.org/10.1038/pr.2015.119"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/psp4.12144", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006052616"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/psp4.12144", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006052616"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2125.1998.00830.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008880155"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0928-0987(99)00037-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010398530"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/00498250600683197", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011379243"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cpt.409", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011663972"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.114.056929", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012440505"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/jpet.113.212258", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012639935"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/psp.2013.55", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012771990"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bdd.1937", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013035265"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/psp4.33", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013084365"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jps.24373", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014001390"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1460-9592.2010.03323.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016655127"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/clpt.2012.19", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016986181", 
          "https://doi.org/10.1038/clpt.2012.19"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-200645090-00005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017122603", 
          "https://doi.org/10.2165/00003088-200645090-00005"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-200645090-00005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017122603", 
          "https://doi.org/10.2165/00003088-200645090-00005"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/bcp.12211", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017356394"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2217/pgs.13.94", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018364234"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00005176-200010000-00019", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019825710"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00005176-200010000-00019", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019825710"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10928-012-9241-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024191422", 
          "https://doi.org/10.1007/s10928-012-9241-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.111.040352", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025773727"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.addr.2013.10.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031730467"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s40262-014-0140-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032278121", 
          "https://doi.org/10.1007/s40262-014-0140-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jcph.585", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032372041"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cpt.449", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033491583"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cpt.176", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034776204"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cpt.176", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034776204"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1136/gut.15.2.151", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035140094"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.116.072652", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035385072"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s40495-016-0059-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038103764", 
          "https://doi.org/10.1007/s40495-016-0059-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s40495-016-0059-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038103764", 
          "https://doi.org/10.1007/s40495-016-0059-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s40495-016-0059-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038103764", 
          "https://doi.org/10.1007/s40495-016-0059-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1208/s12248-014-9592-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038788685", 
          "https://doi.org/10.1208/s12248-014-9592-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.xphs.2016.06.026", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040982685"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/bcp.12234", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041758926"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1208/s12248-016-9896-z", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043062633", 
          "https://doi.org/10.1208/s12248-016-9896-z"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/074823379701300401", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043959433"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/074823379701300401", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043959433"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/clpt.2012.64", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044005735", 
          "https://doi.org/10.1038/clpt.2012.64"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00467-008-0997-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045216032", 
          "https://doi.org/10.1007/s00467-008-0997-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00467-008-0997-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045216032", 
          "https://doi.org/10.1007/s00467-008-0997-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.106.011387", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050551682"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00005176-199107000-00008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050629364"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00005176-199107000-00008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050629364"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1208/s12248-016-9956-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050988427", 
          "https://doi.org/10.1208/s12248-016-9956-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1208/s12248-016-9956-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050988427", 
          "https://doi.org/10.1208/s12248-016-9956-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.115.068643", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052073128"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.05136-11", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062709752"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1152/ajprenal.2001.281.2.f197", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074850582"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1076633253", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ijpharm.2017.05.011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085213748"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.117.076851", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091784251"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1208/s12248-017-0149-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092051363", 
          "https://doi.org/10.1208/s12248-017-0149-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cpt.905", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092192294"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-12", 
    "datePublishedReg": "2018-12-01", 
    "description": "This article provides a brief overview of the development of pediatric physiologically based pharmacokinetic (PPBPK) models, the challenges of uncertain systems information, and finally performance verification considering recent regulatory guidance. Pediatric PBPK (PPBPK) model can incorporate varied manifolds of drug and developmental system information to predict drug PK in children. Health authorities have been receiving a growing number of drug submissions that have used PPBPK. According to a recent review of the FDA office of Clinical Pharmacology, PPBPK modeling has been readily applied for dose regimen selection in a variety of pediatric patient groups via a \u201clearn and confirm\u201d approach. Before applying to pediatrics, a PBPK model is developed using physicochemical, biopharmaceutical, and metabolic parameters of drug and then verified by pharmacokinetics (PK) data in adults. Once the drug parameters are optimized, they can be used in the PPBPK model which contains the \u2018systemic\u2019 data of physiology and biochemistry in children. The drug absorption, distribution, metabolism, and excretion (ADME) parameters can be estimated according to developmental changes in physiology and biochemistry in various age groups of children. The model is then applied to simulate the exposure in children. The current challenge is the paucity of available pediatric systems information and oral biopharmaceutics. They are essential to verify PPBPK models and predict PK particularly in neonates and young infants. The recent research on intestinal and hepatic transporter ontogeny, via mRNA and proteomic data, gives us increased understanding of pediatric drug absorption, hepatic uptake, and biliary excretion. Nevertheless, more validated developmental \u2018system\u2019 data is needed in this field. Another gap is the lack of good quality pediatric drug studies performed across the age range, which currently is a limitation to the performance verification of PPBPK models. PPBPK models have already improved the pediatric drug development process but the important challenges lie ahead. Further development and verification are constantly required. It may be possible to minimize the number of pediatric subjects used in PK studies and avoid some studies altogether.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1007/s40495-018-0162-1", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1051247", 
        "issn": [
          "2198-641X"
        ], 
        "name": "Current Pharmacology Reports", 
        "type": "Periodical"
      }
    ], 
    "name": "Pediatric Physiologically Based Pharmacokinetic Model Development: Current Status and Challenges", 
    "pagination": "1-11", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "c16b58e05516569592eecf2c5290514350bcea7414d77090c478262c6193057c"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s40495-018-0162-1"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1110345002"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s40495-018-0162-1", 
      "https://app.dimensions.ai/details/publication/pub.1110345002"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T08:18", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000281_0000000281/records_9859_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1007%2Fs40495-018-0162-1"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s40495-018-0162-1'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s40495-018-0162-1'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s40495-018-0162-1'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s40495-018-0162-1'


 

This table displays all metadata directly associated to this object as RDF triples.

238 TRIPLES      21 PREDICATES      75 URIs      17 LITERALS      5 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s40495-018-0162-1 schema:about anzsrc-for:11
2 anzsrc-for:1115
3 schema:author Nb1e9f05a455a431cbac6db3126eae061
4 schema:citation sg:pub.10.1007/s00467-008-0997-5
5 sg:pub.10.1007/s10928-012-9241-9
6 sg:pub.10.1007/s11095-015-1762-7
7 sg:pub.10.1007/s40262-014-0140-7
8 sg:pub.10.1007/s40495-016-0059-9
9 sg:pub.10.1038/clpt.2012.19
10 sg:pub.10.1038/clpt.2012.64
11 sg:pub.10.1038/clpt.2012.68
12 sg:pub.10.1038/pr.2015.119
13 sg:pub.10.1208/s12248-014-9592-9
14 sg:pub.10.1208/s12248-016-9896-z
15 sg:pub.10.1208/s12248-016-9956-4
16 sg:pub.10.1208/s12248-017-0149-6
17 sg:pub.10.2165/00003088-200645090-00005
18 https://app.dimensions.ai/details/publication/pub.1076633253
19 https://doi.org/10.1002/bdd.1937
20 https://doi.org/10.1002/cpt.176
21 https://doi.org/10.1002/cpt.409
22 https://doi.org/10.1002/cpt.449
23 https://doi.org/10.1002/cpt.905
24 https://doi.org/10.1002/jcph.585
25 https://doi.org/10.1002/jps.24373
26 https://doi.org/10.1002/psp4.12144
27 https://doi.org/10.1002/psp4.33
28 https://doi.org/10.1016/j.addr.2013.10.006
29 https://doi.org/10.1016/j.ijpharm.2017.05.011
30 https://doi.org/10.1016/j.xphs.2016.06.026
31 https://doi.org/10.1016/s0928-0987(99)00037-8
32 https://doi.org/10.1038/psp.2013.55
33 https://doi.org/10.1046/j.1365-2125.1998.00830.x
34 https://doi.org/10.1080/00498250600683197
35 https://doi.org/10.1097/00005176-199107000-00008
36 https://doi.org/10.1097/00005176-200010000-00019
37 https://doi.org/10.1111/bcp.12211
38 https://doi.org/10.1111/bcp.12234
39 https://doi.org/10.1111/j.1460-9592.2010.03323.x
40 https://doi.org/10.1111/j.1460-9592.2011.03782.x
41 https://doi.org/10.1124/dmd.106.011387
42 https://doi.org/10.1124/dmd.111.040352
43 https://doi.org/10.1124/dmd.114.056929
44 https://doi.org/10.1124/dmd.115.068643
45 https://doi.org/10.1124/dmd.116.069559
46 https://doi.org/10.1124/dmd.116.072652
47 https://doi.org/10.1124/dmd.117.076851
48 https://doi.org/10.1124/jpet.113.212258
49 https://doi.org/10.1128/aac.05136-11
50 https://doi.org/10.1136/gut.15.2.151
51 https://doi.org/10.1152/ajprenal.2001.281.2.f197
52 https://doi.org/10.1177/074823379701300401
53 https://doi.org/10.2217/pgs.13.94
54 schema:datePublished 2018-12
55 schema:datePublishedReg 2018-12-01
56 schema:description This article provides a brief overview of the development of pediatric physiologically based pharmacokinetic (PPBPK) models, the challenges of uncertain systems information, and finally performance verification considering recent regulatory guidance. Pediatric PBPK (PPBPK) model can incorporate varied manifolds of drug and developmental system information to predict drug PK in children. Health authorities have been receiving a growing number of drug submissions that have used PPBPK. According to a recent review of the FDA office of Clinical Pharmacology, PPBPK modeling has been readily applied for dose regimen selection in a variety of pediatric patient groups via a “learn and confirm” approach. Before applying to pediatrics, a PBPK model is developed using physicochemical, biopharmaceutical, and metabolic parameters of drug and then verified by pharmacokinetics (PK) data in adults. Once the drug parameters are optimized, they can be used in the PPBPK model which contains the ‘systemic’ data of physiology and biochemistry in children. The drug absorption, distribution, metabolism, and excretion (ADME) parameters can be estimated according to developmental changes in physiology and biochemistry in various age groups of children. The model is then applied to simulate the exposure in children. The current challenge is the paucity of available pediatric systems information and oral biopharmaceutics. They are essential to verify PPBPK models and predict PK particularly in neonates and young infants. The recent research on intestinal and hepatic transporter ontogeny, via mRNA and proteomic data, gives us increased understanding of pediatric drug absorption, hepatic uptake, and biliary excretion. Nevertheless, more validated developmental ‘system’ data is needed in this field. Another gap is the lack of good quality pediatric drug studies performed across the age range, which currently is a limitation to the performance verification of PPBPK models. PPBPK models have already improved the pediatric drug development process but the important challenges lie ahead. Further development and verification are constantly required. It may be possible to minimize the number of pediatric subjects used in PK studies and avoid some studies altogether.
57 schema:genre research_article
58 schema:inLanguage en
59 schema:isAccessibleForFree false
60 schema:isPartOf sg:journal.1051247
61 schema:name Pediatric Physiologically Based Pharmacokinetic Model Development: Current Status and Challenges
62 schema:pagination 1-11
63 schema:productId N4be5dc3910b44199bf1fd6b91f3e4f86
64 N79c9dbc175544dc4a5614e2c604d2f46
65 Nae859070990246ccaec8cafabd4ebb37
66 schema:sameAs https://app.dimensions.ai/details/publication/pub.1110345002
67 https://doi.org/10.1007/s40495-018-0162-1
68 schema:sdDatePublished 2019-04-11T08:18
69 schema:sdLicense https://scigraph.springernature.com/explorer/license/
70 schema:sdPublisher N5f75dd6611b442ffbd4b79a417e8f6c4
71 schema:url https://link.springer.com/10.1007%2Fs40495-018-0162-1
72 sgo:license sg:explorer/license/
73 sgo:sdDataset articles
74 rdf:type schema:ScholarlyArticle
75 N114f88d83bdc4b5687322dc0016190da rdf:first sg:person.0747467571.02
76 rdf:rest Ncba9e8e30ca949efb22a39bcbe2bbcc1
77 N4be5dc3910b44199bf1fd6b91f3e4f86 schema:name doi
78 schema:value 10.1007/s40495-018-0162-1
79 rdf:type schema:PropertyValue
80 N5a0491689cbd44bf9077174e94f60fb3 rdf:first sg:person.0673341315.60
81 rdf:rest rdf:nil
82 N5f75dd6611b442ffbd4b79a417e8f6c4 schema:name Springer Nature - SN SciGraph project
83 rdf:type schema:Organization
84 N79c9dbc175544dc4a5614e2c604d2f46 schema:name dimensions_id
85 schema:value pub.1110345002
86 rdf:type schema:PropertyValue
87 Nae859070990246ccaec8cafabd4ebb37 schema:name readcube_id
88 schema:value c16b58e05516569592eecf2c5290514350bcea7414d77090c478262c6193057c
89 rdf:type schema:PropertyValue
90 Nb1e9f05a455a431cbac6db3126eae061 rdf:first sg:person.01063055771.51
91 rdf:rest N114f88d83bdc4b5687322dc0016190da
92 Ncba9e8e30ca949efb22a39bcbe2bbcc1 rdf:first sg:person.01012730002.36
93 rdf:rest N5a0491689cbd44bf9077174e94f60fb3
94 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
95 schema:name Medical and Health Sciences
96 rdf:type schema:DefinedTerm
97 anzsrc-for:1115 schema:inDefinedTermSet anzsrc-for:
98 schema:name Pharmacology and Pharmaceutical Sciences
99 rdf:type schema:DefinedTerm
100 sg:journal.1051247 schema:issn 2198-641X
101 schema:name Current Pharmacology Reports
102 rdf:type schema:Periodical
103 sg:person.01012730002.36 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
104 schema:familyName Heimbach
105 schema:givenName Tycho
106 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01012730002.36
107 rdf:type schema:Person
108 sg:person.01063055771.51 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
109 schema:familyName Lin
110 schema:givenName Wen
111 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01063055771.51
112 rdf:type schema:Person
113 sg:person.0673341315.60 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
114 schema:familyName He
115 schema:givenName Handan
116 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0673341315.60
117 rdf:type schema:Person
118 sg:person.0747467571.02 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
119 schema:familyName Yan
120 schema:givenName Jing-He
121 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0747467571.02
122 rdf:type schema:Person
123 sg:pub.10.1007/s00467-008-0997-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045216032
124 https://doi.org/10.1007/s00467-008-0997-5
125 rdf:type schema:CreativeWork
126 sg:pub.10.1007/s10928-012-9241-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024191422
127 https://doi.org/10.1007/s10928-012-9241-9
128 rdf:type schema:CreativeWork
129 sg:pub.10.1007/s11095-015-1762-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003501773
130 https://doi.org/10.1007/s11095-015-1762-7
131 rdf:type schema:CreativeWork
132 sg:pub.10.1007/s40262-014-0140-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032278121
133 https://doi.org/10.1007/s40262-014-0140-7
134 rdf:type schema:CreativeWork
135 sg:pub.10.1007/s40495-016-0059-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038103764
136 https://doi.org/10.1007/s40495-016-0059-9
137 rdf:type schema:CreativeWork
138 sg:pub.10.1038/clpt.2012.19 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016986181
139 https://doi.org/10.1038/clpt.2012.19
140 rdf:type schema:CreativeWork
141 sg:pub.10.1038/clpt.2012.64 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044005735
142 https://doi.org/10.1038/clpt.2012.64
143 rdf:type schema:CreativeWork
144 sg:pub.10.1038/clpt.2012.68 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004025588
145 https://doi.org/10.1038/clpt.2012.68
146 rdf:type schema:CreativeWork
147 sg:pub.10.1038/pr.2015.119 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005211732
148 https://doi.org/10.1038/pr.2015.119
149 rdf:type schema:CreativeWork
150 sg:pub.10.1208/s12248-014-9592-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038788685
151 https://doi.org/10.1208/s12248-014-9592-9
152 rdf:type schema:CreativeWork
153 sg:pub.10.1208/s12248-016-9896-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1043062633
154 https://doi.org/10.1208/s12248-016-9896-z
155 rdf:type schema:CreativeWork
156 sg:pub.10.1208/s12248-016-9956-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050988427
157 https://doi.org/10.1208/s12248-016-9956-4
158 rdf:type schema:CreativeWork
159 sg:pub.10.1208/s12248-017-0149-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092051363
160 https://doi.org/10.1208/s12248-017-0149-6
161 rdf:type schema:CreativeWork
162 sg:pub.10.2165/00003088-200645090-00005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017122603
163 https://doi.org/10.2165/00003088-200645090-00005
164 rdf:type schema:CreativeWork
165 https://app.dimensions.ai/details/publication/pub.1076633253 schema:CreativeWork
166 https://doi.org/10.1002/bdd.1937 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013035265
167 rdf:type schema:CreativeWork
168 https://doi.org/10.1002/cpt.176 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034776204
169 rdf:type schema:CreativeWork
170 https://doi.org/10.1002/cpt.409 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011663972
171 rdf:type schema:CreativeWork
172 https://doi.org/10.1002/cpt.449 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033491583
173 rdf:type schema:CreativeWork
174 https://doi.org/10.1002/cpt.905 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092192294
175 rdf:type schema:CreativeWork
176 https://doi.org/10.1002/jcph.585 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032372041
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1002/jps.24373 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014001390
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1002/psp4.12144 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006052616
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1002/psp4.33 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013084365
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1016/j.addr.2013.10.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031730467
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1016/j.ijpharm.2017.05.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085213748
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1016/j.xphs.2016.06.026 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040982685
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1016/s0928-0987(99)00037-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010398530
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1038/psp.2013.55 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012771990
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1046/j.1365-2125.1998.00830.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1008880155
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1080/00498250600683197 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011379243
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1097/00005176-199107000-00008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050629364
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1097/00005176-200010000-00019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019825710
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1111/bcp.12211 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017356394
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1111/bcp.12234 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041758926
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1111/j.1460-9592.2010.03323.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1016655127
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1111/j.1460-9592.2011.03782.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1005207943
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1124/dmd.106.011387 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050551682
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1124/dmd.111.040352 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025773727
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1124/dmd.114.056929 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012440505
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1124/dmd.115.068643 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052073128
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1124/dmd.116.069559 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004594547
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1124/dmd.116.072652 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035385072
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1124/dmd.117.076851 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091784251
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1124/jpet.113.212258 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012639935
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1128/aac.05136-11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062709752
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1136/gut.15.2.151 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035140094
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1152/ajprenal.2001.281.2.f197 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074850582
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1177/074823379701300401 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043959433
233 rdf:type schema:CreativeWork
234 https://doi.org/10.2217/pgs.13.94 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018364234
235 rdf:type schema:CreativeWork
236 https://www.grid.ac/institutes/grid.418424.f schema:alternateName Novartis (United States)
237 schema:name PK Sciences, Novartis Institutes for Biomedical Research, 07936, East Hanover, NJ, USA
238 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...