{"id":"67c6a6cb-95ef-5c17-8e60-cb1b1512c049","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:rifampicin-raises-atorvastatin-exposure","predicate":"increases","statement":"A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"803ca03f-f263-53dd-8485-9a1c4551f1ee","mechanism_event_label":"A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.","subject":{"id":"72ddad1c-1e7f-5ba7-b078-9a6cf385b4b5","slug":"rifampicin","display_name":"Rifampicin","entity_type_key":"small_molecule"},"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":"803ca03f-f263-53dd-8485-9a1c4551f1ee","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:rifampicin-raises-atorvastatin-exposure-event","event_type":"observed_relationship","label":"A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.","description":"A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"72ddad1c-1e7f-5ba7-b078-9a6cf385b4b5","slug":"rifampicin","display_name":"Rifampicin","entity_type_key":"small_molecule"},"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":"38b2f200-15ca-5db6-8d7e-2b78ee490eda","slug":"slco1b1","display_name":"Human OATP1B1 / SLCO1B1","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":"Single dose, sampling to 24 hours","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":"11 healthy human volunteers, randomised crossover","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Two 40 mg oral atorvastatin doses one week apart, with one 30-minute intravenous infusion of 600 mg rifampicin on one of the two study days","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Rifampicin is used here as a model hepatic uptake inhibitor and is not selective for OATP1B1; the lactone forms rose less than the acid, and a single intravenous dose avoids the enzyme induction that repeated oral rifampicin would cause.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"11 healthy human volunteers, randomised crossover","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral atorvastatin with intravenous rifampicin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Plasma atorvastatin acid and its hydroxy metabolites","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"41a8650b-f797-514b-9f0a-8fceb4af36fa","evidence_kind":"source_excerpt","locator":"Lines 13-22","start_line":13,"end_line":22,"excerpt":"## rifampicin-raises-atorvastatin-exposure\nA single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.\nModel/species: 11 healthy human volunteers, randomised crossover\nTissue/system: Plasma atorvastatin acid and its hydroxy metabolites\nExposure: Two 40 mg oral atorvastatin doses one week apart, with one 30-minute intravenous infusion of 600 mg rifampicin on one of the two study days\nRoute: Oral atorvastatin with intravenous rifampicin\nDuration: Single dose, sampling to 24 hours\nLimits: Rifampicin is used here as a model hepatic uptake inhibitor and is not selective for OATP1B1; the lactone forms rose less than the acid, and a single intravenous dose avoids the enzyme induction that repeated oral rifampicin would cause.\nPrimary reference: The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038\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":"4364bb7b-5a18-5bda-a4bc-0e2a698ab2c6","stable_key":"import-dcb39377-0ae6-5994-8378-19d8aa9baabd","title":"OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. 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