{"@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/1362262943434744960.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1002/hep.23317"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fhep.23317"}},{"identifier":{"@type":"URI","@value":"https://journals.lww.com/01515467-201002000-00032"}}],"dc:title":[{"@value":"Oral Medications With Significant Hepatic Metabolism at Higher Risk for Hepatic Adverse Events"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:sec>\n                    <jats:title/>\n                    <jats:p>\n                      <jats:bold>Reactive metabolites generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury (DILI), but supporting data are limited. If this is true, then compounds with significant hepatic metabolism should cause more DILI than those without it. We conducted a study to examine the relationship between hepatic metabolism and DILI of prescription medications. We systematically extracted the metabolism characteristics of 207 of the most widely prescribed oral medications in the United States. Compounds with >50% hepatic metabolism were characterized as those with significant hepatic metabolism (n = 149). Hepatic adverse events of interest were alanine aminotransferase >3 times the upper limit of normal, jaundice, liver failure, liver transplantation, or fatal DILI. Compared with compounds with lesser hepatic metabolism, compounds belonging to the significant hepatic metabolism group had significantly higher frequency of alanine aminotransferase >3 times the upper limit of normal (35% versus 11%,</jats:bold>\n                      <jats:bold>P</jats:bold>\n                      <jats:bold>= 0.001), liver failure (28% versus 9%,</jats:bold>\n                      <jats:bold>P</jats:bold>\n                      <jats:bold>= 0.004), and fatal DILI (23% versus 4%,</jats:bold>\n                      <jats:bold>P</jats:bold>\n                      <jats:bold>= 0.001), but not jaundice (46% versus 35%,</jats:bold>\n                      <jats:bold>P</jats:bold>\n                      <jats:bold>= 0.2) or liver transplantation (9% versus 2%,</jats:bold>\n                      <jats:bold>P</jats:bold>\n                      <jats:bold>= 0.11). Twelve compounds with no hepatic metabolism had no reports of liver failure, liver transplantation, or fatal DILI. When the relationship between hepatic adverse events and combination of hepatic metabolism and daily dose was examined, compounds with both significant hepatic metabolism and daily dose >50 mg (n = 50) were significantly more hepatotoxic than compounds belonging to other groups. Compared with medications without biliary excretion, compounds with biliary excretion (n = 50) had significantly higher frequency of jaundice (74% versus 40%,</jats:bold>\n                      <jats:bold>P</jats:bold>\n                      <jats:bold>= 0.0001).</jats:bold>\n                      <jats:bold>Conclusion:</jats:bold>\n                      <jats:bold>Our study finds an important relationship between a compound's metabolism profile and reports of hepatic adverse events. (Hepatology 2009.)</jats:bold>\n                    </jats:p>\n                  </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382262943434744960","@type":"Researcher","foaf:name":[{"@value":"Craig Lammert"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943434744963","@type":"Researcher","foaf:name":[{"@value":"Einar Bjornsson"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943434744961","@type":"Researcher","foaf:name":[{"@value":"Anna Niklasson"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943434744962","@type":"Researcher","foaf:name":[{"@value":"Naga Chalasani"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"02709139"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/02709139"}],"prism:publicationName":[{"@value":"Hepatology"}],"dc:publisher":[{"@value":"Ovid Technologies (Wolters Kluwer Health)"}],"prism:publicationDate":"2010-02","prism:volume":"51","prism:number":"2","prism:startingPage":"615","prism:endingPage":"620"},"reviewed":"false","dc:rights":["http://doi.wiley.com/10.1002/tdm_license_1.1"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fhep.23317"},{"@id":"https://journals.lww.com/01515467-201002000-00032"}],"createdAt":"2009-09-14","modifiedAt":"2025-02-11","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004232519668864","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Metabolic activation of hepatotoxic drug (benzbromarone) induced mitochondrial membrane permeability transition"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285710588048384","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Changing etiologies and outcomes of acute liver failure: A perspective from Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565165225801088","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565165969019648","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"CHOP is a critical regulator of acetaminophen-induced hepatotoxicity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567187492807552","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Visualization of Acute Liver Damage Induced by Cycloheximide in Rats Using PET with [18F]FEDAC, a Radiotracer for Translocator Protein (18 kDa)"}]},{"@id":"https://cir.nii.ac.jp/crid/1360576118810553344","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Identification of average molecular weight (AMW) as a useful chemical descriptor to discriminate liver injury-inducing drugs"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584340701272320","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Utility of human cytochrome P450 inhibition data in the assessment of drug-induced liver injury"}]},{"@id":"https://cir.nii.ac.jp/crid/1361134273560904192","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Establishment of a primary human hepatocyte spheroid system for evaluating metabolic toxicity using dacarbazine under conditions of CYP1A2 induction"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001277362441088","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Liver dysfunction induced by Levothyroxine Sodium Tablets (Euthyrox®) in a hypothyroid patient with Hashimoto’s thyroiditis: case report and literature review"}]},{"@id":"https://cir.nii.ac.jp/crid/1390846609792845696","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Usefulness and limitations of mRNA measurement in HepaRG cells for evaluation of cytochrome P450 induction"}]},{"@id":"https://cir.nii.ac.jp/crid/1390855898098124544","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"CREB is a potential marker associated with drug-induced liver injury: Identification and validation through transcriptome database 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