{"id":"https://openalex.org/W3134554074","doi":"https://doi.org/10.1371/journal.pcbi.1008786","title":"Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children","display_name":"Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children","publication_year":2021,"publication_date":"2021-03-04","ids":{"openalex":"https://openalex.org/W3134554074","doi":"https://doi.org/10.1371/journal.pcbi.1008786","mag":"3134554074","pmid":"https://pubmed.ncbi.nlm.nih.gov/33661919"},"language":"en","primary_location":{"id":"doi:10.1371/journal.pcbi.1008786","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1008786","pdf_url":null,"source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1371/journal.pcbi.1008786","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5028090836","display_name":"Laurens F. M. Verscheijden","orcid":"https://orcid.org/0000-0003-0303-898X"},"institutions":[{"id":"https://openalex.org/I145872427","display_name":"Radboud University Nijmegen","ror":"https://ror.org/016xsfp80","country_code":"NL","type":"education","lineage":["https://openalex.org/I145872427"]},{"id":"https://openalex.org/I2802934949","display_name":"Radboud University Medical Center","ror":"https://ror.org/05wg1m734","country_code":"NL","type":"funder","lineage":["https://openalex.org/I2802934949"]},{"id":"https://openalex.org/I4210109357","display_name":"Radboud Institute for Molecular Life Sciences","ror":"https://ror.org/01yb10j39","country_code":"NL","type":"facility","lineage":["https://openalex.org/I145872427","https://openalex.org/I4210109357"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Laurens F. M. Verscheijden","raw_affiliation_strings":["Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0003-0303-898X","affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands","institution_ids":["https://openalex.org/I145872427","https://openalex.org/I2802934949","https://openalex.org/I4210109357"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010179995","display_name":"Carlijn H. C. Litjens","orcid":"https://orcid.org/0000-0003-2743-5090"},"institutions":[{"id":"https://openalex.org/I145872427","display_name":"Radboud University Nijmegen","ror":"https://ror.org/016xsfp80","country_code":"NL","type":"education","lineage":["https://openalex.org/I145872427"]},{"id":"https://openalex.org/I2802934949","display_name":"Radboud University Medical Center","ror":"https://ror.org/05wg1m734","country_code":"NL","type":"funder","lineage":["https://openalex.org/I2802934949"]},{"id":"https://openalex.org/I4210109357","display_name":"Radboud Institute for Molecular Life Sciences","ror":"https://ror.org/01yb10j39","country_code":"NL","type":"facility","lineage":["https://openalex.org/I145872427","https://openalex.org/I4210109357"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Carlijn H. C. Litjens","raw_affiliation_strings":["Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands","Department of Pharmacy, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0003-2743-5090","affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands","institution_ids":["https://openalex.org/I145872427","https://openalex.org/I2802934949","https://openalex.org/I4210109357"]},{"raw_affiliation_string":"Department of Pharmacy, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands","institution_ids":["https://openalex.org/I145872427","https://openalex.org/I2802934949"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Jan B. Koenderink","orcid":null},"institutions":[{"id":"https://openalex.org/I145872427","display_name":"Radboud University Nijmegen","ror":"https://ror.org/016xsfp80","country_code":"NL","type":"education","lineage":["https://openalex.org/I145872427"]},{"id":"https://openalex.org/I2802934949","display_name":"Radboud University Medical Center","ror":"https://ror.org/05wg1m734","country_code":"NL","type":"funder","lineage":["https://openalex.org/I2802934949"]},{"id":"https://openalex.org/I4210109357","display_name":"Radboud Institute for Molecular Life Sciences","ror":"https://ror.org/01yb10j39","country_code":"NL","type":"facility","lineage":["https://openalex.org/I145872427","https://openalex.org/I4210109357"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Jan B. Koenderink","raw_affiliation_strings":["Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands","institution_ids":["https://openalex.org/I145872427","https://openalex.org/I2802934949","https://openalex.org/I4210109357"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074174053","display_name":"Ron H.J. Mathijssen","orcid":"https://orcid.org/0000-0001-5667-5697"},"institutions":[{"id":"https://openalex.org/I4210149908","display_name":"Erasmus MC Cancer Institute","ror":"https://ror.org/03r4m3349","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2801952686","https://openalex.org/I4210149908"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Ron H. J. Mathijssen","raw_affiliation_strings":["Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands","institution_ids":["https://openalex.org/I4210149908"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008603484","display_name":"Marcel M. Verbeek","orcid":"https://orcid.org/0000-0003-4635-7876"},"institutions":[{"id":"https://openalex.org/I145872427","display_name":"Radboud University Nijmegen","ror":"https://ror.org/016xsfp80","country_code":"NL","type":"education","lineage":["https://openalex.org/I145872427"]},{"id":"https://openalex.org/I2802934949","display_name":"Radboud University Medical Center","ror":"https://ror.org/05wg1m734","country_code":"NL","type":"funder","lineage":["https://openalex.org/I2802934949"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Marcel M. Verbeek","raw_affiliation_strings":["Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands","institution_ids":["https://openalex.org/I145872427","https://openalex.org/I2802934949"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074206527","display_name":"Saskia N. de Wildt","orcid":"https://orcid.org/0000-0002-0502-0647"},"institutions":[{"id":"https://openalex.org/I145872427","display_name":"Radboud University Nijmegen","ror":"https://ror.org/016xsfp80","country_code":"NL","type":"education","lineage":["https://openalex.org/I145872427"]},{"id":"https://openalex.org/I2802934949","display_name":"Radboud University Medical Center","ror":"https://ror.org/05wg1m734","country_code":"NL","type":"funder","lineage":["https://openalex.org/I2802934949"]},{"id":"https://openalex.org/I4210109357","display_name":"Radboud Institute for Molecular Life Sciences","ror":"https://ror.org/01yb10j39","country_code":"NL","type":"facility","lineage":["https://openalex.org/I145872427","https://openalex.org/I4210109357"]},{"id":"https://openalex.org/I4210142620","display_name":"Erasmus MC - Sophia Children\u2019s Hospital","ror":"https://ror.org/047afsm11","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2801952686","https://openalex.org/I4210142620"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Saskia N. de Wildt","raw_affiliation_strings":["Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands","Intensive Care and Department of Paediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-0502-0647","affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands","institution_ids":["https://openalex.org/I145872427","https://openalex.org/I2802934949","https://openalex.org/I4210109357"]},{"raw_affiliation_string":"Intensive Care and Department of Paediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands","institution_ids":["https://openalex.org/I4210142620"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5008048278","display_name":"Frans G. M. R\u00fcssel","orcid":"https://orcid.org/0000-0002-7959-2314"},"institutions":[{"id":"https://openalex.org/I145872427","display_name":"Radboud University Nijmegen","ror":"https://ror.org/016xsfp80","country_code":"NL","type":"education","lineage":["https://openalex.org/I145872427"]},{"id":"https://openalex.org/I2802934949","display_name":"Radboud University Medical Center","ror":"https://ror.org/05wg1m734","country_code":"NL","type":"funder","lineage":["https://openalex.org/I2802934949"]},{"id":"https://openalex.org/I4210109357","display_name":"Radboud Institute for Molecular Life Sciences","ror":"https://ror.org/01yb10j39","country_code":"NL","type":"facility","lineage":["https://openalex.org/I145872427","https://openalex.org/I4210109357"]}],"countries":["NL"],"is_corresponding":true,"raw_author_name":"Frans G. M. Russel","raw_affiliation_strings":["Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-7959-2314","affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands","institution_ids":["https://openalex.org/I145872427","https://openalex.org/I2802934949","https://openalex.org/I4210109357"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":7,"corresponding_author_ids":["https://openalex.org/A5008048278"],"corresponding_institution_ids":["https://openalex.org/I145872427","https://openalex.org/I2802934949","https://openalex.org/I4210109357"],"apc_list":{"value":2655,"currency":"USD","value_usd":2655},"apc_paid":{"value":2655,"currency":"USD","value_usd":2655},"fwci":3.1449,"has_fulltext":true,"cited_by_count":27,"citation_normalized_percentile":{"value":0.92212884,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":94,"max":99},"biblio":{"volume":"17","issue":"3","first_page":"e1008786","last_page":"e1008786"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10094","display_name":"Epilepsy research and treatment","score":0.9997000098228455,"subfield":{"id":"https://openalex.org/subfields/2738","display_name":"Psychiatry and Mental health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10094","display_name":"Epilepsy research and treatment","score":0.9997000098228455,"subfield":{"id":"https://openalex.org/subfields/2738","display_name":"Psychiatry and Mental health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.9997000098228455,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10189","display_name":"Anesthesia and Pain Management","score":0.9987000226974487,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/morphine","display_name":"Morphine","score":0.8801789283752441},{"id":"https://openalex.org/keywords/pharmacodynamics","display_name":"Pharmacodynamics","score":0.7550250291824341},{"id":"https://openalex.org/keywords/pharmacology","display_name":"Pharmacology","score":0.720678985118866},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"Pharmacokinetics","score":0.6793016791343689},{"id":"https://openalex.org/keywords/analgesic","display_name":"Analgesic","score":0.6295764446258545},{"id":"https://openalex.org/keywords/opioid","display_name":"Opioid","score":0.5560365915298462},{"id":"https://openalex.org/keywords/in-vivo","display_name":"In vivo","score":0.5234653353691101},{"id":"https://openalex.org/keywords/active-metabolite","display_name":"Active metabolite","score":0.5146063566207886},{"id":"https://openalex.org/keywords/metabolite","display_name":"Metabolite","score":0.5019557476043701},{"id":"https://openalex.org/keywords/medicine","display_name":"Medicine","score":0.48762598633766174},{"id":"https://openalex.org/keywords/drug","display_name":"Drug","score":0.426454097032547},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.3541104197502136},{"id":"https://openalex.org/keywords/internal-medicine","display_name":"Internal medicine","score":0.18718260526657104},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.16561365127563477},{"id":"https://openalex.org/keywords/receptor","display_name":"Receptor","score":0.0731901228427887}],"concepts":[{"id":"https://openalex.org/C2777389121","wikidata":"https://www.wikidata.org/wiki/Q81225","display_name":"Morphine","level":2,"score":0.8801789283752441},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.7550250291824341},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.720678985118866},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.6793016791343689},{"id":"https://openalex.org/C2780820201","wikidata":"https://www.wikidata.org/wiki/Q173235","display_name":"Analgesic","level":2,"score":0.6295764446258545},{"id":"https://openalex.org/C2781063702","wikidata":"https://www.wikidata.org/wiki/Q427523","display_name":"Opioid","level":3,"score":0.5560365915298462},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.5234653353691101},{"id":"https://openalex.org/C149151106","wikidata":"https://www.wikidata.org/wiki/Q4677569","display_name":"Active metabolite","level":3,"score":0.5146063566207886},{"id":"https://openalex.org/C2777477808","wikidata":"https://www.wikidata.org/wiki/Q407595","display_name":"Metabolite","level":2,"score":0.5019557476043701},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.48762598633766174},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.426454097032547},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3541104197502136},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.18718260526657104},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.16561365127563477},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.0731901228427887},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000367","descriptor_name":"Age Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000367","descriptor_name":"Age Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000367","descriptor_name":"Age Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000698","descriptor_name":"Analgesia","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000698","descriptor_name":"Analgesia","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000698","descriptor_name":"Analgesia","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000701","descriptor_name":"Analgesics, Opioid","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D001812","descriptor_name":"Blood-Brain Barrier","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D001812","descriptor_name":"Blood-Brain Barrier","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D001812","descriptor_name":"Blood-Brain Barrier","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D001921","descriptor_name":"Brain","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D001921","descriptor_name":"Brain","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D001921","descriptor_name":"Brain","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002648","descriptor_name":"Child","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002648","descriptor_name":"Child","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002648","descriptor_name":"Child","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002675","descriptor_name":"Child, Preschool","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002675","descriptor_name":"Child, Preschool","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002675","descriptor_name":"Child, Preschool","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007231","descriptor_name":"Infant, Newborn","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007231","descriptor_name":"Infant, Newborn","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007231","descriptor_name":"Infant, Newborn","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D009022","descriptor_name":"Morphine Derivatives","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020168","descriptor_name":"ATP Binding Cassette Transporter, Subfamily B, Member 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D020168","descriptor_name":"ATP Binding Cassette Transporter, Subfamily B, Member 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D020168","descriptor_name":"ATP Binding Cassette Transporter, Subfamily B, Member 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false}],"locations_count":8,"locations":[{"id":"doi:10.1371/journal.pcbi.1008786","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1008786","pdf_url":null,"source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},{"id":"pmid:33661919","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/33661919","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLoS computational biology","raw_type":null},{"id":"pmh:eur:oai:pure.eur.nl:publications/f9227b4f-11c2-4bb0-880f-f0a785a324b5","is_oa":true,"landing_page_url":"https://pure.eur.nl/en/publications/f9227b4f-11c2-4bb0-880f-f0a785a324b5","pdf_url":null,"source":{"id":"https://openalex.org/S4306401843","display_name":"Data Archiving and Networked Services (DANS)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1322597698","host_organization_name":"Royal Netherlands Academy of Arts and Sciences","host_organization_lineage":["https://openalex.org/I1322597698"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLoS Computational Biology, 17(3):e1008786. Public Library of Science","raw_type":"info:eu-repo/semantics/article"},{"id":"pmh:oai:pubmedcentral.nih.gov:7963108","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7963108","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLoS Comput Biol","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:453e7f115c204fa085ec5f77bb94a806","is_oa":true,"landing_page_url":"https://doaj.org/article/453e7f115c204fa085ec5f77bb94a806","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Computational Biology, Vol 17, Iss 3, p e1008786 (2021)","raw_type":"article"},{"id":"pmh:oai:pure.eur.nl:publications/f9227b4f-11c2-4bb0-880f-f0a785a324b5","is_oa":true,"landing_page_url":"http://www.scopus.com/inward/record.url?scp=85102624303&partnerID=8YFLogxK","pdf_url":null,"source":{"id":"https://openalex.org/S4306401266","display_name":"EUR Research Repository (Erasmus University Rotterdam)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I913958620","host_organization_name":"Erasmus University Rotterdam","host_organization_lineage":["https://openalex.org/I913958620"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":""},{"id":"pmh:oai:repository.ubn.ru.nl:2066/232078","is_oa":false,"landing_page_url":"https://repository.ubn.ru.nl/handle/2066/232078","pdf_url":null,"source":{"id":"https://openalex.org/S4306401067","display_name":"Radboud Repository (Radboud University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I145872427","host_organization_name":"Radboud University Nijmegen","host_organization_lineage":["https://openalex.org/I145872427"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Plos Computational Biology, 17, 3","raw_type":"Article / Letter to editor"},{"id":"pmh:ru:oai:repository.ubn.ru.nl:2066/232078","is_oa":true,"landing_page_url":"http://hdl.handle.net/2066/232078","pdf_url":null,"source":{"id":"https://openalex.org/S4306401843","display_name":"Data Archiving and Networked Services (DANS)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1322597698","host_organization_name":"Royal Netherlands Academy of Arts and Sciences","host_organization_lineage":["https://openalex.org/I1322597698"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Plos Computational Biology, 17","raw_type":"info:eu-repo/semantics/article"}],"best_oa_location":{"id":"doi:10.1371/journal.pcbi.1008786","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1008786","pdf_url":null,"source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.7599999904632568,"display_name":"Good health and well-being"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":87,"referenced_works":["https://openalex.org/W1530217337","https://openalex.org/W1939474735","https://openalex.org/W1966739276","https://openalex.org/W1972294202","https://openalex.org/W1972808762","https://openalex.org/W1983821157","https://openalex.org/W1987198534","https://openalex.org/W1994224597","https://openalex.org/W2007732431","https://openalex.org/W2007855905","https://openalex.org/W2008566814","https://openalex.org/W2023187279","https://openalex.org/W2025875656","https://openalex.org/W2030185084","https://openalex.org/W2034887368","https://openalex.org/W2037005814","https://openalex.org/W2040668587","https://openalex.org/W2045728091","https://openalex.org/W2046281206","https://openalex.org/W2052434601","https://openalex.org/W2055207564","https://openalex.org/W2055683699","https://openalex.org/W2057256367","https://openalex.org/W2059636317","https://openalex.org/W2067024737","https://openalex.org/W2074524706","https://openalex.org/W2076865101","https://openalex.org/W2080113500","https://openalex.org/W2081188112","https://openalex.org/W2089580511","https://openalex.org/W2090945850","https://openalex.org/W2094725656","https://openalex.org/W2103372915","https://openalex.org/W2104755278","https://openalex.org/W2106389283","https://openalex.org/W2113830209","https://openalex.org/W2121696198","https://openalex.org/W2124166031","https://openalex.org/W2128396525","https://openalex.org/W2132341968","https://openalex.org/W2134086028","https://openalex.org/W2134457072","https://openalex.org/W2136053754","https://openalex.org/W2136487679","https://openalex.org/W2136564762","https://openalex.org/W2140470640","https://openalex.org/W2145362317","https://openalex.org/W2149440337","https://openalex.org/W2151153010","https://openalex.org/W2154634960","https://openalex.org/W2161723770","https://openalex.org/W2165334931","https://openalex.org/W2168086897","https://openalex.org/W2168923194","https://openalex.org/W2169794329","https://openalex.org/W2170609216","https://openalex.org/W2186287946","https://openalex.org/W2206619362","https://openalex.org/W2213706664","https://openalex.org/W2253617808","https://openalex.org/W2256951323","https://openalex.org/W2329671310","https://openalex.org/W2396366530","https://openalex.org/W2426588295","https://openalex.org/W2491089466","https://openalex.org/W2560422329","https://openalex.org/W2597356561","https://openalex.org/W2752331950","https://openalex.org/W2753592087","https://openalex.org/W2754610420","https://openalex.org/W2767617726","https://openalex.org/W2768615318","https://openalex.org/W2780558190","https://openalex.org/W2790992838","https://openalex.org/W2809590864","https://openalex.org/W2884217236","https://openalex.org/W2913686494","https://openalex.org/W2917680118","https://openalex.org/W2947319191","https://openalex.org/W2949613766","https://openalex.org/W2972717137","https://openalex.org/W2977244096","https://openalex.org/W2977342340","https://openalex.org/W3001382188","https://openalex.org/W3014529563","https://openalex.org/W3027257567","https://openalex.org/W3028368598"],"related_works":["https://openalex.org/W2266355837","https://openalex.org/W2144732297","https://openalex.org/W4236374741","https://openalex.org/W1954166975","https://openalex.org/W2100508540","https://openalex.org/W1973267410","https://openalex.org/W2009214735","https://openalex.org/W2409945781","https://openalex.org/W2156949091","https://openalex.org/W2473041548"],"abstract_inverted_index":{"Morphine":[0],"is":[1],"a":[2,68,207,216],"widely":[3],"used":[4],"opioid":[5],"analgesic,":[6],"which":[7,104,280],"shows":[8],"large":[9],"differences":[10,285],"in":[11,14,37,56,78,88,99,129,148,164,206,212,286],"clinical":[12],"response":[13],"children,":[15,279],"even":[16],"when":[17],"aiming":[18],"for":[19,230,239,250],"equivalent":[20],"plasma":[21],"drug":[22,162,268],"concentrations.":[23],"Age-dependent":[24],"brain":[25,70,150,210,220,254,267],"disposition":[26],"of":[27,62,112,144,196,253],"morphine":[28,66,84,113,136,145,182,245],"could":[29,225],"contribute":[30],"to":[31,271,275],"this":[32],"variability,":[33],"as":[34,158,160],"developmental":[35,106],"increase":[36],"blood-brain":[38],"barrier":[39],"(BBB)":[40],"P-glycoprotein":[41],"(Pgp)":[42],"expression":[43],"has":[44],"been":[45],"reported.":[46],"In":[47,241,259],"addition,":[48],"age-related":[49],"pharmacodynamics":[50],"might":[51],"also":[52],"explain":[53,282],"the":[54,60,202,251,260,283],"variability":[55],"effect.":[57,288],"To":[58],"assess":[59],"influence":[61],"these":[63],"processes":[64],"on":[65,92,219],"effectiveness,":[67],"multi-compartment":[69],"physiologically":[71],"based":[72],"pharmacokinetic/pharmacodynamic":[73],"(PB-PK/PD)":[74],"model":[75,204,247],"was":[76,86,248],"developed":[77,249],"R":[79],"(Version":[80],"3.6.2).":[81],"Active":[82],"Pgp-mediated":[83,198],"transport":[85,200],"measured":[87,140,181],"MDCKII-Pgp":[89],"cells":[90],"grown":[91],"transwell":[93],"filters":[94],"and":[95,114,120,141,146,154,170,180,183,187,193,233,256,277],"translated":[96],"by":[97],"an":[98,243],"vitro-in":[100],"vivo":[101],"extrapolation":[102],"approach,":[103],"included":[105],"Pgp":[107],"expression.":[108],"Passive":[109],"BBB":[110,199],"permeability":[111],"its":[115],"active":[116,197],"metabolite":[117],"morphine-6-glucuronide":[118],"(M6G)":[119],"their":[121],"pharmacodynamic":[122,263],"parameters":[123],"were":[124,137,190,236],"derived":[125],"from":[126],"experiments":[127],"reported":[128,284],"literature.":[130],"Model":[131],"simulations":[132],"after":[133],"single":[134],"dose":[135],"compared":[138,274],"with":[139],"published":[142,161],"concentrations":[143],"M6G":[147,184],"plasma,":[149],"extracellular":[151],"fluid":[152,156],"(ECF)":[153],"cerebrospinal":[155],"(CSF),":[157],"well":[159,229],"responses":[163],"children":[165,232],"(1":[166],"day-":[167],"16":[168],"years)":[169],"adults.":[171],"Visual":[172],"predictive":[173],"checks":[174],"indicated":[175],"acceptable":[176],"overlays":[177],"between":[178,191],"simulated":[179],"concentration-time":[185],"profiles":[186,224],"prediction":[188,252],"errors":[189],"1":[192],"-1.":[194],"Incorporation":[195],"into":[201],"PB-PK/PD":[203,246],"resulted":[205],"1.3-fold":[208],"reduced":[209],"exposure":[211],"adults,":[213,234],"indicating":[214],"only":[215],"modest":[217],"contribution":[218],"disposition.":[221],"Analgesic":[222],"effect-time":[223],"be":[226,272],"described":[227],"reasonably":[228],"older":[231,278],"but":[235,265],"largely":[237],"underpredicted":[238],"neonates.":[240],"summary,":[242],"age-appropriate":[244],"pharmacokinetics":[255],"analgesic":[257,287],"effects.":[258],"neonatal":[261],"population,":[262],"characteristics,":[264],"not":[266],"disposition,":[269],"appear":[270],"altered":[273],"adults":[276],"may":[281]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":8},{"year":2023,"cited_by_count":4},{"year":2022,"cited_by_count":7},{"year":2021,"cited_by_count":2}],"updated_date":"2026-05-21T06:26:12.895304","created_date":"2025-10-10T00:00:00"}
