{"id":"https://openalex.org/W7216525639","doi":"https://doi.org/10.3390/pharmaceutics18101254","title":"PBPK Modeling Investigation of IVIVE\u2013Observed Pharmacokinetic Divergence for VU0467319: A Mechanistic Refinement Workflow for Low-Solubility Compounds","display_name":"PBPK Modeling Investigation of IVIVE\u2013Observed Pharmacokinetic Divergence for VU0467319: A Mechanistic Refinement Workflow for Low-Solubility Compounds","publication_year":2026,"publication_date":"2026-10-02","ids":{"openalex":"https://openalex.org/W7216525639","doi":"https://doi.org/10.3390/pharmaceutics18101254","pmid":"https://pubmed.ncbi.nlm.nih.gov/42942786","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13708466"},"language":"en","primary_location":{"id":"doi:10.3390/pharmaceutics18101254","doi":"https://doi.org/10.3390/pharmaceutics18101254","is_oa":true,"landing_page_url":"https://doi.org/10.3390/pharmaceutics18101254","pdf_url":null,"source":{"id":"https://openalex.org/S30283931","display_name":"Pharmaceutics","issn_l":"1999-4923","issn":["1999-4923"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Pharmaceutics","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3390/pharmaceutics18101254","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5133287924","display_name":"Akinwunmi A. Abisogun","orcid":"https://orcid.org/0009-0000-0498-4201","observed_orcids":["https://orcid.org/0009-0000-0498-4201"]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Akinwunmi A. Abisogun","raw_affiliation_strings":["Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, TN 37232, USA","Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"],"raw_orcid":"https://orcid.org/0009-0000-0498-4201","affiliations":[{"raw_affiliation_string":"Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111187789","display_name":"Srinivasan Krishnan","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Srinivasan Krishnan","raw_affiliation_strings":["Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA","Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, TN 37232, USA","Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060483072","display_name":"Craig W. Lindsley","orcid":"https://orcid.org/0000-0003-0168-1445","observed_orcids":["https://orcid.org/0000-0003-0168-1445"]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Craig W. Lindsley","raw_affiliation_strings":["Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA","Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, TN 37232, USA","Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5075984448","display_name":"Olivier G. Boutaud","orcid":"https://orcid.org/0000-0002-8910-0598","observed_orcids":["https://orcid.org/0000-0002-8910-0598"]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Olivier Boutaud","raw_affiliation_strings":["Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA","Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, TN 37232, USA","Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"],"raw_orcid":"https://orcid.org/0000-0002-8910-0598","affiliations":[{"raw_affiliation_string":"Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA","institution_ids":["https://openalex.org/I200719446"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5075984448"],"corresponding_institution_ids":["https://openalex.org/I200719446"],"apc_list":{"value":2900,"currency":"CHF","value_usd":3499},"apc_paid":{"value":2900,"currency":"CHF","value_usd":3499},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.68215583,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"18","issue":"10","first_page":"1254","last_page":"1254"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10256","display_name":"Drug Solubulity and Delivery Systems","score":0.4961000084877014,"subfield":{"id":"https://openalex.org/subfields/3003","display_name":"Pharmaceutical Science"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10256","display_name":"Drug Solubulity and Delivery Systems","score":0.4961000084877014,"subfield":{"id":"https://openalex.org/subfields/3003","display_name":"Pharmaceutical Science"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12547","display_name":"Pharmaceutical studies and practices","score":0.38179999589920044,"subfield":{"id":"https://openalex.org/subfields/2735","display_name":"Pediatrics, Perinatology and Child 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/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.03840000182390213,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/physiologically-based-pharmacokinetic-model","display_name":"physiologically based pharmacokinetic modeling","score":0.8930000066757202},{"id":"https://openalex.org/keywords/in-vitro-in-vivo-extrapolation","display_name":"in vitro-in vivo extrapolation","score":0.7730000019073486},{"id":"https://openalex.org/keywords/supersaturation","display_name":"supersaturation","score":0.8159999847412109},{"id":"https://openalex.org/keywords/clearance","display_name":"clearance","score":0.335999995470047},{"id":"https://openalex.org/keywords/distribution","display_name":"distribution","score":0.33000001311302185},{"id":"https://openalex.org/keywords/model-refinement","display_name":"model refinement","score":0.5590000152587891},{"id":"https://openalex.org/keywords/single-ascending-dose","display_name":"single ascending dose","score":0.7310000061988831}],"concepts":[{"id":"https://openalex.org/C185867374","wikidata":"https://www.wikidata.org/wiki/Q2562769","display_name":"Physiologically based pharmacokinetic modelling","level":3,"score":0.9488999843597412},{"id":"https://openalex.org/C69366308","wikidata":"https://www.wikidata.org/wiki/Q2272286","display_name":"ADME","level":3,"score":0.6377999782562256},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.5819000005722046},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5360000133514404},{"id":"https://openalex.org/C207390915","wikidata":"https://www.wikidata.org/wiki/Q1230525","display_name":"Divergence (linguistics)","level":2,"score":0.45719999074935913},{"id":"https://openalex.org/C181389837","wikidata":"https://www.wikidata.org/wiki/Q461809","display_name":"Bioavailability","level":2,"score":0.40380001068115234},{"id":"https://openalex.org/C177212765","wikidata":"https://www.wikidata.org/wiki/Q627335","display_name":"Workflow","level":2,"score":0.38510000705718994},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.36809998750686646},{"id":"https://openalex.org/C107673813","wikidata":"https://www.wikidata.org/wiki/Q812534","display_name":"Bayesian probability","level":2,"score":0.35600000619888306},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3319999873638153},{"id":"https://openalex.org/C137535248","wikidata":"https://www.wikidata.org/wiki/Q4914691","display_name":"Bioanalysis","level":2,"score":0.30649998784065247},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.29660001397132874},{"id":"https://openalex.org/C91602232","wikidata":"https://www.wikidata.org/wiki/Q756115","display_name":"Volatility (finance)","level":2,"score":0.29490000009536743},{"id":"https://openalex.org/C160234255","wikidata":"https://www.wikidata.org/wiki/Q812535","display_name":"Bayesian inference","level":3,"score":0.27959999442100525},{"id":"https://openalex.org/C99844830","wikidata":"https://www.wikidata.org/wiki/Q102441924","display_name":"Scaling","level":2,"score":0.2705000042915344},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.259799987077713},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.25940001010894775},{"id":"https://openalex.org/C125287762","wikidata":"https://www.wikidata.org/wiki/Q1758948","display_name":"Absorption (acoustics)","level":2,"score":0.25679999589920044},{"id":"https://openalex.org/C2776239304","wikidata":"https://www.wikidata.org/wiki/Q6954915","display_name":"NONMEM","level":3,"score":0.2563000023365021}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.3390/pharmaceutics18101254","doi":"https://doi.org/10.3390/pharmaceutics18101254","is_oa":true,"landing_page_url":"https://doi.org/10.3390/pharmaceutics18101254","pdf_url":null,"source":{"id":"https://openalex.org/S30283931","display_name":"Pharmaceutics","issn_l":"1999-4923","issn":["1999-4923"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Pharmaceutics","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13708466","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13708466/","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13708466/pdf/pharmaceutics-18-01254.pdf","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,"listed_in":[],"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":"Pharmaceutics","raw_type":"Text"},{"id":"pmid:42942786","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42942786","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,"listed_in":[],"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":"Pharmaceutics","raw_type":"Journal Article"},{"id":"pmh:oai:doaj.org/article:2cf3b7a5ad514468ad89129cd603f0bd","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/2cf3b7a5ad514468ad89129cd603f0bd","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,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Pharmaceutics, Vol 18, Iss 10, p 1254 (2026)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3390/pharmaceutics18101254","doi":"https://doi.org/10.3390/pharmaceutics18101254","is_oa":true,"landing_page_url":"https://doi.org/10.3390/pharmaceutics18101254","pdf_url":null,"source":{"id":"https://openalex.org/S30283931","display_name":"Pharmaceutics","issn_l":"1999-4923","issn":["1999-4923"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Pharmaceutics","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.8371999859809875,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G9000875921","display_name":"Clinical Pharmacology Training Program","funder_award_id":"T32GM007569","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7216525639.pdf","grobid_xml":"https://content.openalex.org/works/W7216525639.grobid-xml"},"referenced_works_count":16,"referenced_works":["https://openalex.org/W1603855465","https://openalex.org/W1996949498","https://openalex.org/W2006967678","https://openalex.org/W2027143209","https://openalex.org/W2028165836","https://openalex.org/W2039250788","https://openalex.org/W2512897046","https://openalex.org/W2912877386","https://openalex.org/W4389607752","https://openalex.org/W4401519512","https://openalex.org/W4402892131","https://openalex.org/W4403403100","https://openalex.org/W4405276255","https://openalex.org/W4405438701","https://openalex.org/W4411894989","https://openalex.org/W4413115372"],"related_works":["https://openalex.org/W7126183431","https://openalex.org/W1641607484","https://openalex.org/W2742371482","https://openalex.org/W1549457774","https://openalex.org/W2914645825","https://openalex.org/W164365017","https://openalex.org/W2767793633","https://openalex.org/W2909814037","https://openalex.org/W7117235105","https://openalex.org/W2135772015"],"abstract_inverted_index":{"Background/Objectives:":[0],"VU0467319":[1],"(VU319),":[2],"an":[3],"M1":[4],"muscarinic":[5],"positive":[6],"allosteric":[7],"modulator":[8],"evaluated":[9,85],"in":[10,55,60],"Phase":[11],"1":[12,127],"studies,":[13],"exhibits":[14],"subproportional":[15],"dose-exposure":[16,199],"scaling":[17],"typical":[18],"of":[19,35,76,104,162],"poorly":[20],"soluble":[21],"compounds.":[22],"This":[23],"study":[24],"applies":[25],"physiologically":[26],"based":[27],"pharmacokinetic":[28,67],"(PBPK)":[29],"modeling":[30],"to":[31,95,120,187,225],"investigate":[32],"the":[33,110,145,171,181,189,196,220],"sources":[34],"divergence":[36,227],"between":[37],"IVIVE-based":[38],"predictions":[39],"and":[40,63,79,125,157,209,235],"observed":[41,111,197,263],"single":[42],"ascending":[43],"dose":[44],"(SAD)":[45],"clinical":[46,98],"pharmacokinetics.":[47,264],"Methods:":[48],"A":[49,101],"whole-body":[50],"PBPK":[51,214],"model":[52,74,107,139,194],"was":[53,84,185],"developed":[54],"Simcyp":[56],"Simulator":[57],"V24":[58],"using":[59,90],"vitro":[61],"ADME":[62],"physicochemical":[64],"inputs.":[65],"Clinical":[66],"data":[68],"were":[69],"used":[70],"for":[71,155,159,228,254],"sequential,":[72],"hypothesis-driven":[73],"refinement":[75,215,252],"distribution,":[77],"clearance,":[78],"absorption":[80,218],"parameters.":[81],"Model":[82],"performance":[83,142],"at":[86,170,207],"60\u2013600":[87],"mg":[88],"fasted":[89],"virtual":[91],"populations":[92],"demographically":[93],"matched":[94],"their":[96],"corresponding":[97],"cohort.":[99],"Results:":[100],"Kp":[102],"scalar":[103],"0.125":[105],"recovered":[106,131],"Vss":[108],"within":[109,133,165,180],"Vz/F":[112],"bound;":[113],"a":[114,126,250],"10.7-fold":[115],"downward":[116],"CLint":[117],"correction":[118],"(32.2":[119],"3":[121],"\u00b5L/min/mg)":[122],"reconciled":[123],"clearance;":[124],"\u00b5m":[128],"particle":[129],"radius":[130],"AUC0\u2013\u221e":[132],"6%":[134],"across":[135,144],"60\u2013240":[136],"mg.":[137,211],"The":[138,192,246],"met":[140],"predefined":[141],"thresholds":[143],"four":[146,163],"independent":[147],"verification":[148],"doses":[149,164,173],"(geometric":[150],"mean":[151],"fold":[152],"error":[153],"1.45":[154],"AUC":[156],"1.56":[158],"Cmax;":[160],"three":[161],"2-fold),":[166],"with":[167,230],"progressive":[168],"underprediction":[169],"highest":[172],"(\u2265400":[174],"mg).":[175],"Supersaturation-ratio":[176],"analysis":[177],"indicated":[178],"that,":[179],"model,":[182],"sustained":[183],"supersaturation":[184],"unlikely":[186],"explain":[188],"high-dose":[190],"underprediction.":[191],"refined":[193],"reproduced":[195],"sub-proportional":[198],"relationship":[200],"through":[201],"240":[202],"mg,":[203],"but":[204],"underpredicted":[205],"exposure":[206],"400":[208],"600":[210],"Conclusions:":[212],"Structured":[213],"identified":[216],"dissolution-limited":[217],"as":[219],"most":[221],"likely":[222],"primary":[223],"contributor":[224],"IVIVE\u2013observed":[226],"VU319,":[229],"secondary":[231],"contributions":[232],"from":[233,262],"clearance":[234],"distribution.":[236],"These":[237],"model-derived":[238],"mechanisms":[239],"remain":[240],"hypotheses":[241],"that":[242],"require":[243],"experimental":[244],"confirmation.":[245],"workflow":[247],"may":[248],"provide":[249],"structured":[251],"framework":[253],"other":[255],"low-solubility":[256],"compounds":[257],"where":[258],"IVIVE":[259],"assumptions":[260],"diverge":[261]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2026-10-03T00:00:00"}
