{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360021396521388160.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1002/cpt.2829"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/cpt.2829"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cpt.2829"}},{"identifier":{"@type":"URI","@value":"https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/cpt.2829"}}],"dc:title":[{"@value":"Effect of Hepatic Impairment on <scp>OATP1B</scp> Activity: Quantitative Pharmacokinetic Analysis of Endogenous Biomarker and Substrate Drugs"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Hepatic impairment (HI) is known to modulate drug disposition and may lead to elevated plasma exposure. The aim of this study was to quantitate the <jats:italic>in vivo</jats:italic> OATP1B‐mediated hepatic uptake activity in populations with varying degrees of HI. First, we measured baseline levels of plasma coproporphyrin‐I, an endogenous OATP1B biomarker, in an open‐label, parallel cohort study in adult subjects with normal liver function and mild, moderate, and severe HI (<jats:italic>n</jats:italic> = 24, 6/cohort). The geometric mean plasma concentrations of coproporphyrin‐I were 1.66‐fold, 2.81‐fold (<jats:italic>P</jats:italic> < 0.05), and 7.78‐fold (<jats:italic>P</jats:italic> < 0.0001) higher in mild, moderate, and severe impairment than those healthy controls. Second, we developed a dataset of 21 OATP1B substrate drugs with HI data extracted from literature. Median disease‐to‐healthy plasma area under the curve (AUC) ratios for substrate drugs were ~ 1.4, 3.0, and 6.4 for mild, moderate, and severe HI, respectively. Additionally, significant linear relationship was noted between AUC ratios of substrate drugs without and with co‐administration of rifampin, a prototypic OATP1B inhibitor, and AUC ratios in moderate (<jats:italic>P</jats:italic> < 0.01) and severe (<jats:italic>P</jats:italic> < 0.001) HI. Third, a physiologically‐based pharmacokinetic model analysis was conducted with 10 substrate drugs following estimation of relative OATP1B functional activity in virtual disease population models using coproporphyrin‐I data and verification of substrate models with rifampin drug–drug interaction data. This approach adequately predicted plasma AUC change particularly in moderate (9 of 10 within 2‐fold) and severe (5 of 5 within 2‐fold) HI. Collective findings indicate progressive reduction, by as much as 90–92%, in OATP1B activity in the HI population.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380021396521388163","@type":"Researcher","foaf:name":[{"@value":"Jian Lin"}],"jpcoar:affiliationName":[{"@value":"Pharmacokinetics, Dynamics and Metabolism, Medicine Design Worldwide R&D, Pfizer Inc  Groton Connecticut USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396521388162","@type":"Researcher","foaf:name":[{"@value":"Emi Kimoto"}],"jpcoar:affiliationName":[{"@value":"Pharmacokinetics, Dynamics and Metabolism, Medicine Design Worldwide R&D, Pfizer Inc  Groton Connecticut USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396521388166","@type":"Researcher","foaf:name":[{"@value":"Shinji Yamazaki"}],"jpcoar:affiliationName":[{"@value":"Pharmacokinetics, Dynamics and Metabolism, Medicine Design Worldwide R&D, Pfizer Inc.  San Diego California USA"},{"@value":"Drug Metabolism and Pharmacokinetics Janssen Research & Development, LLC  San Diego California USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396521388165","@type":"Researcher","foaf:name":[{"@value":"Manoli Vourvahis"}],"jpcoar:affiliationName":[{"@value":"Clinical Pharmacology, Global Product Development Pfizer Inc.  New York New York USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396521388168","@type":"Researcher","foaf:name":[{"@value":"Arthur Bergman"}],"jpcoar:affiliationName":[{"@value":"Clinical Pharmacology, Early Clinical Development Pfizer Inc.  Cambridge Massachusetts USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396521388160","@type":"Researcher","foaf:name":[{"@value":"A. David Rodrigues"}],"jpcoar:affiliationName":[{"@value":"Pharmacokinetics, Dynamics and Metabolism, Medicine Design Worldwide R&D, Pfizer Inc  Groton Connecticut USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396521388161","@type":"Researcher","foaf:name":[{"@value":"Chester Costales"}],"jpcoar:affiliationName":[{"@value":"Pharmacokinetics, Dynamics and Metabolism, Medicine Design Worldwide R&D, Pfizer Inc  Groton Connecticut USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396521388164","@type":"Researcher","foaf:name":[{"@value":"Rui Li"}],"jpcoar:affiliationName":[{"@value":"Pharmacokinetics, Dynamics and Metabolism, Medicine Design Worldwide R&D, Pfizer Inc.  Cambridge Massachusetts USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396521388167","@type":"Researcher","foaf:name":[{"@value":"Manthena V. S. Varma"}],"jpcoar:affiliationName":[{"@value":"Pharmacokinetics, Dynamics and Metabolism, Medicine Design Worldwide R&D, Pfizer Inc  Groton Connecticut USA"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00099236"},{"@type":"EISSN","@value":"15326535"}],"prism:publicationName":[{"@value":"Clinical Pharmacology & Therapeutics"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2023-01-15","prism:volume":"113","prism:number":"5","prism:startingPage":"1058","prism:endingPage":"1069"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/cpt.2829"},{"@id":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cpt.2829"},{"@id":"https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/cpt.2829"}],"createdAt":"2022-12-16","modifiedAt":"2023-11-14","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050867819570829952","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Impact of cancer cachexia progression on OATP1B1 transport activity: Quantitative analysis using coproporphyrin-I as an endogenous biomarker"},{"@value":"Impact of Cancer Cachexia Progression on OATP1B1 Transport Activity: Quantitative Analysis Using Coproporphyrin‐I as an Endogenous Biomarker"}]},{"@id":"https://cir.nii.ac.jp/crid/1360025795868305152","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Integrating renal transporter biomarkers into drug development: Discovery, clinical assessment, and precision medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1360026059121353984","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Applications of in vitro transporter assays for mechanistic characterization and prediction of clinical drug-drug interactions"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584340723313408","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"A 20-Year Research Overview: Quantitative Prediction of Hepatic Clearance Using the In Vitro-In Vivo Extrapolation Approach Based on Physiologically Based Pharmacokinetic Modeling and Extended Clearance Concept"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1002/cpt.2829"},{"@type":"CROSSREF","@value":"10.1002/cpt.3649_references_DOI_V3dBSzxqUZ3te20309EJA4hfi0i"},{"@type":"CROSSREF","@value":"10.1016/j.dmpk.2026.101515_references_DOI_V3dBSzxqUZ3te20309EJA4hfi0i"},{"@type":"CROSSREF","@value":"10.1016/j.dmpk.2026.101528_references_DOI_V3dBSzxqUZ3te20309EJA4hfi0i"},{"@type":"CROSSREF","@value":"10.1124/dmd.123.001344_references_DOI_V3dBSzxqUZ3te20309EJA4hfi0i"}]}