{"id":"9dd5bf42-7e32-544f-a8a1-062a566c2e21","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:slco1b1-c521cc-raises-atorvastatin-exposure","predicate":"increases","statement":"Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"3dab6d6a-4eff-5e8b-b6a2-9c482f895feb","mechanism_event_label":"Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.","subject":{"id":"ecd774bf-b45c-553f-b50b-892cf5cca148","slug":"slco1b1-c521tc-variant","display_name":"SLCO1B1 c.521T>C reduced-function variant","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":"3dab6d6a-4eff-5e8b-b6a2-9c482f895feb","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:slco1b1-c521cc-raises-atorvastatin-exposure-event","event_type":"observed_relationship","label":"Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.","description":"Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.","status":"provisional","compartment":null,"participants":[{"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":"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 with 48-hour sampling","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":"32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Single 20 mg oral atorvastatin dose","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Only four participants carried the c.521CC genotype, and 2-hydroxyatorvastatin exposure was 100 percent greater in the same comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. (2007). https://pubmed.ncbi.nlm.nih.gov/17473846/ DOI: 10.1038/sj.clpt.6100220","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Plasma atorvastatin area under the concentration-time curve from 0 to 48 hours","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"63106595-bd40-582b-9b6a-1ce229459b37","evidence_kind":"source_excerpt","locator":"Lines 35-44","start_line":35,"end_line":44,"excerpt":"## slco1b1-c521cc-raises-atorvastatin-exposure\nVolunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.\nModel/species: 32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT\nTissue/system: Plasma atorvastatin area under the concentration-time curve from 0 to 48 hours\nExposure: Single 20 mg oral atorvastatin dose\nRoute: Oral\nDuration: Single dose with 48-hour sampling\nLimits: Only four participants carried the c.521CC genotype, and 2-hydroxyatorvastatin exposure was 100 percent greater in the same comparison.\nPrimary reference: Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. (2007). https://pubmed.ncbi.nlm.nih.gov/17473846/ DOI: 10.1038/sj.clpt.6100220\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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