{"id":"6f7093e2-e8d3-54cf-bb49-362c202790cc","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:cyp3a4-clears-atorvastatin","predicate":"reduces","statement":"Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"6bfa1f9c-099b-5b07-94bb-9b2c89dcc2ca","mechanism_event_label":"Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.","subject":{"id":"4df69614-d899-5299-a999-e891f6298c10","slug":"cyp3a4-activity","display_name":"Human CYP3A4 activity, probe and compartment specified","entity_type_key":"cellular_process"},"object":{"id":"1ff526e8-51cd-5f09-a7fe-93117a7df947","slug":"atorvastatin-plasma-exposure","display_name":"Plasma atorvastatin exposure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6bfa1f9c-099b-5b07-94bb-9b2c89dcc2ca","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:cyp3a4-clears-atorvastatin-event","event_type":"observed_relationship","label":"Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.","description":"Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4df69614-d899-5299-a999-e891f6298c10","slug":"cyp3a4-activity","display_name":"Human CYP3A4 activity, probe and compartment specified","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1ff526e8-51cd-5f09-a7fe-93117a7df947","slug":"atorvastatin-plasma-exposure","display_name":"Plasma atorvastatin exposure","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"222f6587-14d7-5110-902a-f390498c3b12","slug":"cyp3a5","display_name":"Human cytochrome P450 3A5","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"64f4b2c7-afdf-5b9a-b6f9-015a7aa96eee","slug":"atorvastatin","display_name":"Atorvastatin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not applicable","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human liver microsomes and human recombinant CYP3A enzymes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Atorvastatin, enzyme kinetics showing substrate inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The authors conclude the CYP3A5 polymorphism is therefore unlikely to be an important source of between-person variation in atorvastatin disposition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human liver microsomes and human recombinant CYP3A enzymes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. (2008). https://pubmed.ncbi.nlm.nih.gov/18720283/ DOI: 10.1080/00498250802334391","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Hepatic oxidative metabolism","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"669fc336-7dc1-5642-9943-ebbf39cf8e0b","evidence_kind":"source_excerpt","locator":"Lines 144-153","start_line":144,"end_line":153,"excerpt":"## cyp3a4-clears-atorvastatin\nAtorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.\nModel/species: Human liver microsomes and human recombinant CYP3A enzymes\nTissue/system: Hepatic oxidative metabolism\nExposure: Atorvastatin, enzyme kinetics showing substrate inhibition\nRoute: In vitro\nDuration: Not applicable\nLimits: The authors conclude the CYP3A5 polymorphism is therefore unlikely to be an important source of between-person variation in atorvastatin disposition.\nPrimary reference: Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. (2008). https://pubmed.ncbi.nlm.nih.gov/18720283/ DOI: 10.1080/00498250802334391\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a4431d8c-34d7-5db7-9edf-a35f68feba39","stable_key":"import-1fb6218a-60d1-55ea-87fe-07d15d0fc46f","title":"Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"6307f1acf99f90662320328974781ee660348754257b1e1555701ad597edc8e5","revision_id":"447c5978-ba3f-58fe-ac85-664caa72e01b","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}