{"id":"b4bedbef-568f-57a8-8bb6-4f2e938c23ed","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:oatp1b1-activity-lowers-atorvastatin-exposure","predicate":"reduces","statement":"OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"6f98fd1e-89e6-5b95-80cb-d71b96238784","mechanism_event_label":"OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.","subject":{"id":"38b2f200-15ca-5db6-8d7e-2b78ee490eda","slug":"slco1b1","display_name":"Human OATP1B1 / SLCO1B1","entity_type_key":"protein"},"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":"6f98fd1e-89e6-5b95-80cb-d71b96238784","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:oatp1b1-activity-lowers-atorvastatin-exposure-event","event_type":"observed_relationship","label":"OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.","description":"OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38b2f200-15ca-5db6-8d7e-2b78ee490eda","slug":"slco1b1","display_name":"Human OATP1B1 / SLCO1B1","entity_type_key":"protein"},"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":"72ddad1c-1e7f-5ba7-b078-9a6cf385b4b5","slug":"rifampicin","display_name":"Rifampicin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ecd774bf-b45c-553f-b50b-892cf5cca148","slug":"slco1b1-c521tc-variant","display_name":"SLCO1B1 c.521T>C reduced-function variant","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Single dose in both designs","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":"Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Rifampicin inhibition in one study and the SLCO1B1 c.521CC genotype in another","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is the mechanistic reading shared by an inhibitor study and a genotype study rather than a single measurement of transporter activity against exposure; neither study measured OATP1B1 activity directly in the participants.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.","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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Hepatic sinusoidal uptake and systemic plasma exposure","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"dc4f7f0d-8435-50d1-b973-0d6e2af5ee69","evidence_kind":"source_excerpt","locator":"Lines 24-33","start_line":24,"end_line":33,"excerpt":"## oatp1b1-activity-lowers-atorvastatin-exposure\nOATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.\nModel/species: Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype\nTissue/system: Hepatic sinusoidal uptake and systemic plasma exposure\nExposure: Rifampicin inhibition in one study and the SLCO1B1 c.521CC genotype in another\nRoute: Oral atorvastatin\nDuration: Single dose in both designs\nLimits: This is the mechanistic reading shared by an inhibitor study and a genotype study rather than a single measurement of transporter activity against exposure; neither study measured OATP1B1 activity directly in the participants.\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. Not publisher full text.","file_path":"","sha256":"0b274cf63fca0a5f8d12f53ab8bb81e04204bf547dd9dd8eacfc355a34e2bb8a","revision_id":"5544656f-04d1-56d2-9f63-ec1a8bbc4b7f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}