A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-10

AUTHORS

Valentina Shakhnovich, P. Brian Smith, Jeffrey T. Guptill, Laura P. James, David N. Collier, Huali Wu, Chad E. Livingston, Jian Zhao, Gregory L. Kearns, Michael Cohen-Wolkowiez, On behalf of the Best Pharmaceuticals for Children Act–Pediatric Trials Network

ABSTRACT

BACKGROUND AND AIMS: Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for acid-related disease. In a recent multi-center investigation, we demonstrated decreased, total body weight adjusted, apparent clearance (CL/F) of the PPI pantoprazole for obese children compared with their non-obese peers. Subsequently, we developed a population-based pharmacokinetic (PopPK) model to characterize pantoprazole disposition and evaluated appropriate pantoprazole dosing strategies for obese pediatric patients, using simulation. METHODS: Pharmacokinetic data from the only prospective study of PPIs in obese children (aged 6-17 years; n = 40) included 273 pantoprazole and 256 pantoprazole-sulfone plasma concentrations, after single oral-dose administration, and were used for pantoprazole model development and covariate analysis (NONMEM®). Model evaluation was performed via bootstrapping and predictive checks, and the final model was applied to simulate systemic pantoprazole exposures for common dosing scenarios. RESULTS: A two-compartment PopPK model, which included CYP2C19 genotype and total body weight, provided the best fit. Resultant, typical, weight-normalized pantoprazole parameter estimates were different than previously reported for children or adults, with significantly reduced pantoprazole CL/F for obese children. Of the dosing scenarios evaluated, the weight-tiered approach, approved by the US Food and Drug Administration, achieved pantoprazole exposures [area under the curve (AUC0-∞)] within ranges previously reported as therapeutic, without over- or under-prediction for obese children. CONCLUSIONS: Our data argue against empiric dose escalation of PPIs for obese children and support current FDA-approved pediatric weight-tiered dosing for pantoprazole; however, 3- to 5-fold inter-individual variability in pantoprazole AUC0-∞ remained using this dosing approach. More... »

PAGES

483-495

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s40272-018-0305-1

DOI

http://dx.doi.org/10.1007/s40272-018-0305-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1106098117

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30097906


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/2008/1117", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Public Health and Health Services", 
        "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"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "2-Pyridinylmethylsulfinylbenzimidazoles", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Administration, Oral", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adolescent", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Area Under Curve", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Body Weight", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Child", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Metabolic Clearance Rate", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Models, Biological", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Obesity", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Pantoprazole", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prospective Studies", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proton Pump Inhibitors", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Missouri\u2013Kansas City", 
          "id": "https://www.grid.ac/institutes/grid.266756.6", 
          "name": [
            "The Children\u2019s Mercy Hospital, Kansas City, MO, USA", 
            "University of Missouri-Kansas City School of Medicine, Kansas City, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shakhnovich", 
        "givenName": "Valentina", 
        "id": "sg:person.0632440231.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0632440231.27"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Duke University", 
          "id": "https://www.grid.ac/institutes/grid.26009.3d", 
          "name": [
            "Duke Clinical Research Institute, Durham, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Brian Smith", 
        "givenName": "P.", 
        "id": "sg:person.011044217024.71", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011044217024.71"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Duke University", 
          "id": "https://www.grid.ac/institutes/grid.26009.3d", 
          "name": [
            "Duke Clinical Research Institute, Durham, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Guptill", 
        "givenName": "Jeffrey T.", 
        "id": "sg:person.0602446514.12", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0602446514.12"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Arkansas Children's Hospital", 
          "id": "https://www.grid.ac/institutes/grid.239305.e", 
          "name": [
            "Arkansas Children\u2019s Hospital, Little Rock, AR, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "James", 
        "givenName": "Laura P.", 
        "id": "sg:person.01002410337.39", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01002410337.39"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "East Carolina University", 
          "id": "https://www.grid.ac/institutes/grid.255364.3", 
          "name": [
            "East Carolina University, Greenville, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Collier", 
        "givenName": "David N.", 
        "id": "sg:person.01106471035.18", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01106471035.18"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Duke University", 
          "id": "https://www.grid.ac/institutes/grid.26009.3d", 
          "name": [
            "Duke Clinical Research Institute, Durham, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wu", 
        "givenName": "Huali", 
        "id": "sg:person.011713314151.25", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011713314151.25"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Duke University", 
          "id": "https://www.grid.ac/institutes/grid.26009.3d", 
          "name": [
            "Duke Clinical Research Institute, Durham, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Livingston", 
        "givenName": "Chad E.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Emmes Corporation", 
          "id": "https://www.grid.ac/institutes/grid.280434.9", 
          "name": [
            "The Emmes Corporation, Rockville, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhao", 
        "givenName": "Jian", 
        "id": "sg:person.013556500535.63", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013556500535.63"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Arkansas Children's Hospital", 
          "id": "https://www.grid.ac/institutes/grid.239305.e", 
          "name": [
            "Arkansas Children\u2019s Hospital, Little Rock, AR, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kearns", 
        "givenName": "Gregory L.", 
        "id": "sg:person.01300326714.99", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300326714.99"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Duke University", 
          "id": "https://www.grid.ac/institutes/grid.26009.3d", 
          "name": [
            "Duke Clinical Research Institute, Durham, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cohen-Wolkowiez", 
        "givenName": "Michael", 
        "id": "sg:person.01006544654.25", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01006544654.25"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "East Carolina University", 
          "id": "https://www.grid.ac/institutes/grid.255364.3", 
          "name": [
            "East Carolina University, Greenville, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "On behalf of the Best Pharmaceuticals for Children Act\u2013Pediatric Trials Network", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1016/s0169-2607(98)00067-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001860622"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-200544100-00004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003951240", 
          "https://doi.org/10.2165/00003088-200544100-00004"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-200544100-00004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003951240", 
          "https://doi.org/10.2165/00003088-200544100-00004"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/11599410-000000000-00000", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004003598", 
          "https://doi.org/10.2165/11599410-000000000-00000"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/0091270008321811", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004200322"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ajg.2009.632", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006130682", 
          "https://doi.org/10.1038/ajg.2009.632"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ajg.2009.632", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006130682", 
          "https://doi.org/10.1038/ajg.2009.632"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1542/peds.2011-2879", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007487100"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/0091270010390040", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009436811"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1001/jamapediatrics.2015.132", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010786805"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/0091270010366146", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010986200"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3109/17477166.2010.491118", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012738907"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1001/jama.2014.732", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013269363"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2125.1981.tb01163.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013686164"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00128072-200305010-00003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015859829", 
          "https://doi.org/10.2165/00128072-200305010-00003"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00128072-200305010-00003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015859829", 
          "https://doi.org/10.2165/00128072-200305010-00003"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cmpb.2003.11.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016305514"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2133/dmpk.24.25", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016503399"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cmpb.2010.04.018", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017004244"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00228-015-1948-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020840426", 
          "https://doi.org/10.1007/s00228-015-1948-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10928-007-9066-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023254119", 
          "https://doi.org/10.1007/s10928-007-9066-0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/0091270010377501", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023313298"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2253-14-77", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024923738", 
          "https://doi.org/10.1186/1471-2253-14-77"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/bcp.12619", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024940207"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s40262-015-0277-z", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030170087", 
          "https://doi.org/10.1007/s40262-015-0277-z"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-200039030-00004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030572913", 
          "https://doi.org/10.2165/00003088-200039030-00004"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-200039030-00004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030572913", 
          "https://doi.org/10.2165/00003088-200039030-00004"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-pharmtox-010814-124354", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033637432"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jps.23574", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034156008"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00007691-200402000-00006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036913136"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00007691-200402000-00006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036913136"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.02942-15", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038150259"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2133/dmpk.24.145", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040164243"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.clinthera.2015.08.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040750123"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/prp2.131", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041125641"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/bja/aer057", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041834716"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1016/s0009-9236(97)90081-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043912187", 
          "https://doi.org/10.1016/s0009-9236(97)90081-3"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bdd.1863", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044160623"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.clinthera.2015.05.495", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045168633"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1023/a:1012299115260", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050934479", 
          "https://doi.org/10.1023/a:1012299115260"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.5639/gabij.2013.0202.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1073059775"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/cts.12475", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1086030361"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jpeds.2017.10.011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1100590925"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jpeds.2017.10.011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1100590925"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-10", 
    "datePublishedReg": "2018-10-01", 
    "description": "BACKGROUND AND AIMS: Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for acid-related disease. In a recent multi-center investigation, we demonstrated decreased, total body weight adjusted, apparent clearance (CL/F) of the PPI pantoprazole for obese children compared with their non-obese peers. Subsequently, we developed a population-based pharmacokinetic (PopPK) model to characterize pantoprazole disposition and evaluated appropriate pantoprazole dosing strategies for obese pediatric patients, using simulation.\nMETHODS: Pharmacokinetic data from the only prospective study of PPIs in obese children (aged 6-17\u00a0years; n\u2009=\u200940) included 273 pantoprazole and 256 pantoprazole-sulfone plasma concentrations, after single oral-dose administration, and were used for pantoprazole model development and covariate analysis (NONMEM\u00ae). Model evaluation was performed via bootstrapping and predictive checks, and the final model was applied to simulate systemic pantoprazole exposures for common dosing scenarios.\nRESULTS: A two-compartment PopPK model, which included CYP2C19 genotype and total body weight, provided the best fit. Resultant, typical, weight-normalized pantoprazole parameter estimates were different than previously reported for children or adults, with significantly reduced pantoprazole CL/F for obese children. Of the dosing scenarios evaluated, the weight-tiered approach, approved by the US Food and Drug Administration, achieved pantoprazole exposures [area under the curve (AUC0-\u221e)] within ranges previously reported as therapeutic, without over- or under-prediction for obese children.\nCONCLUSIONS: Our data argue against empiric dose escalation of PPIs for obese children and support current FDA-approved pediatric weight-tiered dosing for pantoprazole; however, 3- to 5-fold inter-individual variability in pantoprazole AUC0-\u221e remained using this dosing approach.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1007/s40272-018-0305-1", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2347735", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.5246016", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2684510", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.3802139", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2348129", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1020815", 
        "issn": [
          "1174-5878", 
          "1179-2019"
        ], 
        "name": "Pediatric Drugs", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "5", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "20"
      }
    ], 
    "name": "A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents", 
    "pagination": "483-495", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "964edcf62382f6642c2ad5d1bcb8fa7730d2f498a8171caad31cf33ceaaf5208"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30097906"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "100883685"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s40272-018-0305-1"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1106098117"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s40272-018-0305-1", 
      "https://app.dimensions.ai/details/publication/pub.1106098117"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T12:15", 
    "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/v90/0000000361_0000000361/records_54014_00000001.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1007%2Fs40272-018-0305-1"
  }
]
 

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/s40272-018-0305-1'

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/s40272-018-0305-1'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s40272-018-0305-1'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s40272-018-0305-1'


 

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

344 TRIPLES      21 PREDICATES      82 URIs      36 LITERALS      24 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s40272-018-0305-1 schema:about N0ea124c857e64c7391d0d70a2809e456
2 N340e87227a18475fb906fe131936f7bc
3 N397bad0c5e51475baae68cd3beb33705
4 N771996b2fa1d4a3681b0c0b41ee2e4fc
5 N8899f94b26fa4b60a12fc7df23cc63ab
6 N9cb13cda8a7b4707872ba291c93883bb
7 Nb17656dc4e8946ea802a543ca8d21721
8 Nd287684f46aa4e3e962a2f4504299ab9
9 Nd31052153ebf409ea8733825b73b7946
10 Ne42802e7731f4937b65bacc7ca8d6a8e
11 Ne7e1fbffa5cb4a71a5c21924d8d2c3b6
12 Ne7e77a45600448f68e45ba0ec623d41c
13 Ne9f0f47ca84c4b5db800889641471b90
14 Nf16e063d62594218ab2aa7e76ed69052
15 Nf313baa35ed441afaf000f8cfb4652c4
16 anzsrc-for:11
17 anzsrc-for:1117
18 schema:author Ndc22864c41394e0294081fb89c9c4cc5
19 schema:citation sg:pub.10.1007/s00228-015-1948-2
20 sg:pub.10.1007/s10928-007-9066-0
21 sg:pub.10.1007/s40262-015-0277-z
22 sg:pub.10.1016/s0009-9236(97)90081-3
23 sg:pub.10.1023/a:1012299115260
24 sg:pub.10.1038/ajg.2009.632
25 sg:pub.10.1186/1471-2253-14-77
26 sg:pub.10.2165/00003088-200039030-00004
27 sg:pub.10.2165/00003088-200544100-00004
28 sg:pub.10.2165/00128072-200305010-00003
29 sg:pub.10.2165/11599410-000000000-00000
30 https://doi.org/10.1001/jama.2014.732
31 https://doi.org/10.1001/jamapediatrics.2015.132
32 https://doi.org/10.1002/bdd.1863
33 https://doi.org/10.1002/jps.23574
34 https://doi.org/10.1002/prp2.131
35 https://doi.org/10.1016/j.clinthera.2015.05.495
36 https://doi.org/10.1016/j.clinthera.2015.08.006
37 https://doi.org/10.1016/j.cmpb.2003.11.003
38 https://doi.org/10.1016/j.cmpb.2010.04.018
39 https://doi.org/10.1016/j.jpeds.2017.10.011
40 https://doi.org/10.1016/s0169-2607(98)00067-4
41 https://doi.org/10.1093/bja/aer057
42 https://doi.org/10.1097/00007691-200402000-00006
43 https://doi.org/10.1111/bcp.12619
44 https://doi.org/10.1111/cts.12475
45 https://doi.org/10.1111/j.1365-2125.1981.tb01163.x
46 https://doi.org/10.1128/aac.02942-15
47 https://doi.org/10.1146/annurev-pharmtox-010814-124354
48 https://doi.org/10.1177/0091270008321811
49 https://doi.org/10.1177/0091270010366146
50 https://doi.org/10.1177/0091270010377501
51 https://doi.org/10.1177/0091270010390040
52 https://doi.org/10.1542/peds.2011-2879
53 https://doi.org/10.2133/dmpk.24.145
54 https://doi.org/10.2133/dmpk.24.25
55 https://doi.org/10.3109/17477166.2010.491118
56 https://doi.org/10.5639/gabij.2013.0202.025
57 schema:datePublished 2018-10
58 schema:datePublishedReg 2018-10-01
59 schema:description BACKGROUND AND AIMS: Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for acid-related disease. In a recent multi-center investigation, we demonstrated decreased, total body weight adjusted, apparent clearance (CL/F) of the PPI pantoprazole for obese children compared with their non-obese peers. Subsequently, we developed a population-based pharmacokinetic (PopPK) model to characterize pantoprazole disposition and evaluated appropriate pantoprazole dosing strategies for obese pediatric patients, using simulation. METHODS: Pharmacokinetic data from the only prospective study of PPIs in obese children (aged 6-17 years; n = 40) included 273 pantoprazole and 256 pantoprazole-sulfone plasma concentrations, after single oral-dose administration, and were used for pantoprazole model development and covariate analysis (NONMEM®). Model evaluation was performed via bootstrapping and predictive checks, and the final model was applied to simulate systemic pantoprazole exposures for common dosing scenarios. RESULTS: A two-compartment PopPK model, which included CYP2C19 genotype and total body weight, provided the best fit. Resultant, typical, weight-normalized pantoprazole parameter estimates were different than previously reported for children or adults, with significantly reduced pantoprazole CL/F for obese children. Of the dosing scenarios evaluated, the weight-tiered approach, approved by the US Food and Drug Administration, achieved pantoprazole exposures [area under the curve (AUC0-∞)] within ranges previously reported as therapeutic, without over- or under-prediction for obese children. CONCLUSIONS: Our data argue against empiric dose escalation of PPIs for obese children and support current FDA-approved pediatric weight-tiered dosing for pantoprazole; however, 3- to 5-fold inter-individual variability in pantoprazole AUC0-∞ remained using this dosing approach.
60 schema:genre research_article
61 schema:inLanguage en
62 schema:isAccessibleForFree false
63 schema:isPartOf N195360364b9d44739bb80adf7e010f8d
64 N3d616d86300e44e5bedb7779913f6c57
65 sg:journal.1020815
66 schema:name A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents
67 schema:pagination 483-495
68 schema:productId N131e916d69064ff3a49417fe7bb03663
69 N53ccd213d6be418b8177e8394ff4042a
70 N8d1dfe6a38c247e0864d3cf3a10b840a
71 Ncfe21829f4424c6788ec6246901c271b
72 Nd40b1e56edda4e9089236c7acc07deaf
73 schema:sameAs https://app.dimensions.ai/details/publication/pub.1106098117
74 https://doi.org/10.1007/s40272-018-0305-1
75 schema:sdDatePublished 2019-04-11T12:15
76 schema:sdLicense https://scigraph.springernature.com/explorer/license/
77 schema:sdPublisher N765066eeed80406fa4b2779ed6ed9829
78 schema:url https://link.springer.com/10.1007%2Fs40272-018-0305-1
79 sgo:license sg:explorer/license/
80 sgo:sdDataset articles
81 rdf:type schema:ScholarlyArticle
82 N0ea124c857e64c7391d0d70a2809e456 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
83 schema:name Administration, Oral
84 rdf:type schema:DefinedTerm
85 N131e916d69064ff3a49417fe7bb03663 schema:name doi
86 schema:value 10.1007/s40272-018-0305-1
87 rdf:type schema:PropertyValue
88 N195360364b9d44739bb80adf7e010f8d schema:issueNumber 5
89 rdf:type schema:PublicationIssue
90 N340e87227a18475fb906fe131936f7bc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
91 schema:name 2-Pyridinylmethylsulfinylbenzimidazoles
92 rdf:type schema:DefinedTerm
93 N397bad0c5e51475baae68cd3beb33705 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name Adolescent
95 rdf:type schema:DefinedTerm
96 N3d616d86300e44e5bedb7779913f6c57 schema:volumeNumber 20
97 rdf:type schema:PublicationVolume
98 N523e8af35f3343f898a5836922d7cac4 rdf:first sg:person.0602446514.12
99 rdf:rest Nbb9ae7f24cef43dc85189e22a436d55f
100 N53ccd213d6be418b8177e8394ff4042a schema:name dimensions_id
101 schema:value pub.1106098117
102 rdf:type schema:PropertyValue
103 N765066eeed80406fa4b2779ed6ed9829 schema:name Springer Nature - SN SciGraph project
104 rdf:type schema:Organization
105 N76e84d9187e3453e9a8385ad7e32f593 rdf:first sg:person.01300326714.99
106 rdf:rest Ne95c376b93fe404e88f9035e050a9a42
107 N76f0a92a2d344ef18bc7afd6811bee95 rdf:first sg:person.011044217024.71
108 rdf:rest N523e8af35f3343f898a5836922d7cac4
109 N771996b2fa1d4a3681b0c0b41ee2e4fc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Pantoprazole
111 rdf:type schema:DefinedTerm
112 N7bd0355a35474fd0a678cd6111c32416 rdf:first sg:person.013556500535.63
113 rdf:rest N76e84d9187e3453e9a8385ad7e32f593
114 N872269f737874b02931a5f7bcb98c17a schema:affiliation https://www.grid.ac/institutes/grid.255364.3
115 schema:familyName On behalf of the Best Pharmaceuticals for Children Act–Pediatric Trials Network
116 rdf:type schema:Person
117 N8899f94b26fa4b60a12fc7df23cc63ab schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
118 schema:name Child
119 rdf:type schema:DefinedTerm
120 N8d1dfe6a38c247e0864d3cf3a10b840a schema:name pubmed_id
121 schema:value 30097906
122 rdf:type schema:PropertyValue
123 N9a43d568e064489d9a19e3deb891ca31 schema:affiliation https://www.grid.ac/institutes/grid.26009.3d
124 schema:familyName Livingston
125 schema:givenName Chad E.
126 rdf:type schema:Person
127 N9cb13cda8a7b4707872ba291c93883bb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Body Weight
129 rdf:type schema:DefinedTerm
130 Nb17656dc4e8946ea802a543ca8d21721 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
131 schema:name Area Under Curve
132 rdf:type schema:DefinedTerm
133 Nb1bf920032ab42f8bc70d18c4034aec0 rdf:first sg:person.011713314151.25
134 rdf:rest Ncefc29f014984f0a8237000b9097ece4
135 Nbb9ae7f24cef43dc85189e22a436d55f rdf:first sg:person.01002410337.39
136 rdf:rest Nbc9c9ae90ade4b2caa4f4cc57e33f452
137 Nbc9c9ae90ade4b2caa4f4cc57e33f452 rdf:first sg:person.01106471035.18
138 rdf:rest Nb1bf920032ab42f8bc70d18c4034aec0
139 Nccfbb0528fd148e5b1aefd10658c6a0f rdf:first N872269f737874b02931a5f7bcb98c17a
140 rdf:rest rdf:nil
141 Ncefc29f014984f0a8237000b9097ece4 rdf:first N9a43d568e064489d9a19e3deb891ca31
142 rdf:rest N7bd0355a35474fd0a678cd6111c32416
143 Ncfe21829f4424c6788ec6246901c271b schema:name readcube_id
144 schema:value 964edcf62382f6642c2ad5d1bcb8fa7730d2f498a8171caad31cf33ceaaf5208
145 rdf:type schema:PropertyValue
146 Nd287684f46aa4e3e962a2f4504299ab9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
147 schema:name Female
148 rdf:type schema:DefinedTerm
149 Nd31052153ebf409ea8733825b73b7946 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
150 schema:name Proton Pump Inhibitors
151 rdf:type schema:DefinedTerm
152 Nd40b1e56edda4e9089236c7acc07deaf schema:name nlm_unique_id
153 schema:value 100883685
154 rdf:type schema:PropertyValue
155 Ndc22864c41394e0294081fb89c9c4cc5 rdf:first sg:person.0632440231.27
156 rdf:rest N76f0a92a2d344ef18bc7afd6811bee95
157 Ne42802e7731f4937b65bacc7ca8d6a8e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
158 schema:name Metabolic Clearance Rate
159 rdf:type schema:DefinedTerm
160 Ne7e1fbffa5cb4a71a5c21924d8d2c3b6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name Models, Biological
162 rdf:type schema:DefinedTerm
163 Ne7e77a45600448f68e45ba0ec623d41c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Prospective Studies
165 rdf:type schema:DefinedTerm
166 Ne95c376b93fe404e88f9035e050a9a42 rdf:first sg:person.01006544654.25
167 rdf:rest Nccfbb0528fd148e5b1aefd10658c6a0f
168 Ne9f0f47ca84c4b5db800889641471b90 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
169 schema:name Humans
170 rdf:type schema:DefinedTerm
171 Nf16e063d62594218ab2aa7e76ed69052 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
172 schema:name Male
173 rdf:type schema:DefinedTerm
174 Nf313baa35ed441afaf000f8cfb4652c4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
175 schema:name Obesity
176 rdf:type schema:DefinedTerm
177 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
178 schema:name Medical and Health Sciences
179 rdf:type schema:DefinedTerm
180 anzsrc-for:1117 schema:inDefinedTermSet anzsrc-for:
181 schema:name Public Health and Health Services
182 rdf:type schema:DefinedTerm
183 sg:grant.2347735 http://pending.schema.org/fundedItem sg:pub.10.1007/s40272-018-0305-1
184 rdf:type schema:MonetaryGrant
185 sg:grant.2348129 http://pending.schema.org/fundedItem sg:pub.10.1007/s40272-018-0305-1
186 rdf:type schema:MonetaryGrant
187 sg:grant.2684510 http://pending.schema.org/fundedItem sg:pub.10.1007/s40272-018-0305-1
188 rdf:type schema:MonetaryGrant
189 sg:grant.3802139 http://pending.schema.org/fundedItem sg:pub.10.1007/s40272-018-0305-1
190 rdf:type schema:MonetaryGrant
191 sg:grant.5246016 http://pending.schema.org/fundedItem sg:pub.10.1007/s40272-018-0305-1
192 rdf:type schema:MonetaryGrant
193 sg:journal.1020815 schema:issn 1174-5878
194 1179-2019
195 schema:name Pediatric Drugs
196 rdf:type schema:Periodical
197 sg:person.01002410337.39 schema:affiliation https://www.grid.ac/institutes/grid.239305.e
198 schema:familyName James
199 schema:givenName Laura P.
200 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01002410337.39
201 rdf:type schema:Person
202 sg:person.01006544654.25 schema:affiliation https://www.grid.ac/institutes/grid.26009.3d
203 schema:familyName Cohen-Wolkowiez
204 schema:givenName Michael
205 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01006544654.25
206 rdf:type schema:Person
207 sg:person.011044217024.71 schema:affiliation https://www.grid.ac/institutes/grid.26009.3d
208 schema:familyName Brian Smith
209 schema:givenName P.
210 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011044217024.71
211 rdf:type schema:Person
212 sg:person.01106471035.18 schema:affiliation https://www.grid.ac/institutes/grid.255364.3
213 schema:familyName Collier
214 schema:givenName David N.
215 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01106471035.18
216 rdf:type schema:Person
217 sg:person.011713314151.25 schema:affiliation https://www.grid.ac/institutes/grid.26009.3d
218 schema:familyName Wu
219 schema:givenName Huali
220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011713314151.25
221 rdf:type schema:Person
222 sg:person.01300326714.99 schema:affiliation https://www.grid.ac/institutes/grid.239305.e
223 schema:familyName Kearns
224 schema:givenName Gregory L.
225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300326714.99
226 rdf:type schema:Person
227 sg:person.013556500535.63 schema:affiliation https://www.grid.ac/institutes/grid.280434.9
228 schema:familyName Zhao
229 schema:givenName Jian
230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013556500535.63
231 rdf:type schema:Person
232 sg:person.0602446514.12 schema:affiliation https://www.grid.ac/institutes/grid.26009.3d
233 schema:familyName Guptill
234 schema:givenName Jeffrey T.
235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0602446514.12
236 rdf:type schema:Person
237 sg:person.0632440231.27 schema:affiliation https://www.grid.ac/institutes/grid.266756.6
238 schema:familyName Shakhnovich
239 schema:givenName Valentina
240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0632440231.27
241 rdf:type schema:Person
242 sg:pub.10.1007/s00228-015-1948-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020840426
243 https://doi.org/10.1007/s00228-015-1948-2
244 rdf:type schema:CreativeWork
245 sg:pub.10.1007/s10928-007-9066-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023254119
246 https://doi.org/10.1007/s10928-007-9066-0
247 rdf:type schema:CreativeWork
248 sg:pub.10.1007/s40262-015-0277-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1030170087
249 https://doi.org/10.1007/s40262-015-0277-z
250 rdf:type schema:CreativeWork
251 sg:pub.10.1016/s0009-9236(97)90081-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043912187
252 https://doi.org/10.1016/s0009-9236(97)90081-3
253 rdf:type schema:CreativeWork
254 sg:pub.10.1023/a:1012299115260 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050934479
255 https://doi.org/10.1023/a:1012299115260
256 rdf:type schema:CreativeWork
257 sg:pub.10.1038/ajg.2009.632 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006130682
258 https://doi.org/10.1038/ajg.2009.632
259 rdf:type schema:CreativeWork
260 sg:pub.10.1186/1471-2253-14-77 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024923738
261 https://doi.org/10.1186/1471-2253-14-77
262 rdf:type schema:CreativeWork
263 sg:pub.10.2165/00003088-200039030-00004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030572913
264 https://doi.org/10.2165/00003088-200039030-00004
265 rdf:type schema:CreativeWork
266 sg:pub.10.2165/00003088-200544100-00004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003951240
267 https://doi.org/10.2165/00003088-200544100-00004
268 rdf:type schema:CreativeWork
269 sg:pub.10.2165/00128072-200305010-00003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015859829
270 https://doi.org/10.2165/00128072-200305010-00003
271 rdf:type schema:CreativeWork
272 sg:pub.10.2165/11599410-000000000-00000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004003598
273 https://doi.org/10.2165/11599410-000000000-00000
274 rdf:type schema:CreativeWork
275 https://doi.org/10.1001/jama.2014.732 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013269363
276 rdf:type schema:CreativeWork
277 https://doi.org/10.1001/jamapediatrics.2015.132 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010786805
278 rdf:type schema:CreativeWork
279 https://doi.org/10.1002/bdd.1863 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044160623
280 rdf:type schema:CreativeWork
281 https://doi.org/10.1002/jps.23574 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034156008
282 rdf:type schema:CreativeWork
283 https://doi.org/10.1002/prp2.131 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041125641
284 rdf:type schema:CreativeWork
285 https://doi.org/10.1016/j.clinthera.2015.05.495 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045168633
286 rdf:type schema:CreativeWork
287 https://doi.org/10.1016/j.clinthera.2015.08.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040750123
288 rdf:type schema:CreativeWork
289 https://doi.org/10.1016/j.cmpb.2003.11.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016305514
290 rdf:type schema:CreativeWork
291 https://doi.org/10.1016/j.cmpb.2010.04.018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017004244
292 rdf:type schema:CreativeWork
293 https://doi.org/10.1016/j.jpeds.2017.10.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100590925
294 rdf:type schema:CreativeWork
295 https://doi.org/10.1016/s0169-2607(98)00067-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001860622
296 rdf:type schema:CreativeWork
297 https://doi.org/10.1093/bja/aer057 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041834716
298 rdf:type schema:CreativeWork
299 https://doi.org/10.1097/00007691-200402000-00006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036913136
300 rdf:type schema:CreativeWork
301 https://doi.org/10.1111/bcp.12619 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024940207
302 rdf:type schema:CreativeWork
303 https://doi.org/10.1111/cts.12475 schema:sameAs https://app.dimensions.ai/details/publication/pub.1086030361
304 rdf:type schema:CreativeWork
305 https://doi.org/10.1111/j.1365-2125.1981.tb01163.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1013686164
306 rdf:type schema:CreativeWork
307 https://doi.org/10.1128/aac.02942-15 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038150259
308 rdf:type schema:CreativeWork
309 https://doi.org/10.1146/annurev-pharmtox-010814-124354 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033637432
310 rdf:type schema:CreativeWork
311 https://doi.org/10.1177/0091270008321811 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004200322
312 rdf:type schema:CreativeWork
313 https://doi.org/10.1177/0091270010366146 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010986200
314 rdf:type schema:CreativeWork
315 https://doi.org/10.1177/0091270010377501 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023313298
316 rdf:type schema:CreativeWork
317 https://doi.org/10.1177/0091270010390040 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009436811
318 rdf:type schema:CreativeWork
319 https://doi.org/10.1542/peds.2011-2879 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007487100
320 rdf:type schema:CreativeWork
321 https://doi.org/10.2133/dmpk.24.145 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040164243
322 rdf:type schema:CreativeWork
323 https://doi.org/10.2133/dmpk.24.25 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016503399
324 rdf:type schema:CreativeWork
325 https://doi.org/10.3109/17477166.2010.491118 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012738907
326 rdf:type schema:CreativeWork
327 https://doi.org/10.5639/gabij.2013.0202.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1073059775
328 rdf:type schema:CreativeWork
329 https://www.grid.ac/institutes/grid.239305.e schema:alternateName Arkansas Children's Hospital
330 schema:name Arkansas Children’s Hospital, Little Rock, AR, USA
331 rdf:type schema:Organization
332 https://www.grid.ac/institutes/grid.255364.3 schema:alternateName East Carolina University
333 schema:name East Carolina University, Greenville, NC, USA
334 rdf:type schema:Organization
335 https://www.grid.ac/institutes/grid.26009.3d schema:alternateName Duke University
336 schema:name Duke Clinical Research Institute, Durham, NC, USA
337 rdf:type schema:Organization
338 https://www.grid.ac/institutes/grid.266756.6 schema:alternateName University of Missouri–Kansas City
339 schema:name The Children’s Mercy Hospital, Kansas City, MO, USA
340 University of Missouri-Kansas City School of Medicine, Kansas City, USA
341 rdf:type schema:Organization
342 https://www.grid.ac/institutes/grid.280434.9 schema:alternateName Emmes Corporation
343 schema:name The Emmes Corporation, Rockville, MD, USA
344 rdf:type schema:Organization
 




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


...