{"id":"a9b5dacc-9e99-5fbe-9691-1baa9b87ca33","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:slco1b1-c521cc-raises-simvastatin-acid-exposure","predicate":"increases","statement":"Volunteers with the SLCO1B1 c.521CC genotype had 221 percent greater plasma exposure to active simvastatin acid 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":"291716d7-8112-5ec4-b71e-a2e47af3e6bb","mechanism_event_label":"Volunteers with the SLCO1B1 c.521CC genotype had 221 percent greater plasma exposure to active simvastatin acid 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":"3c530768-ff75-596f-9135-4def848bd08a","slug":"simvastatin-plasma-exposure","display_name":"Plasma simvastatin exposure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"291716d7-8112-5ec4-b71e-a2e47af3e6bb","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:slco1b1-c521cc-raises-simvastatin-acid-exposure-event","event_type":"observed_relationship","label":"Volunteers with the SLCO1B1 c.521CC genotype had 221 percent greater plasma exposure to active simvastatin acid than those with the c.521TT genotype.","description":"Volunteers with the SLCO1B1 c.521CC genotype had 221 percent greater plasma exposure to active simvastatin acid 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":"3c530768-ff75-596f-9135-4def848bd08a","slug":"simvastatin-plasma-exposure","display_name":"Plasma simvastatin 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":"b7de977d-fed9-5b1c-8138-fd951442b067","slug":"simvastatin","display_name":"Simvastatin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Single dose with 12-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":"4 volunteers with c.521CC, 12 with c.521TC and 16 with c.521TT","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Single 40 mg oral simvastatin dose","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Peak concentration was 200 percent higher and occurred earlier in c.521CC carriers; the four-carrier group is small.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"4 volunteers 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 221 percent greater plasma exposure to active simvastatin acid than those with the c.521TT genotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. (2006). https://pubmed.ncbi.nlm.nih.gov/17108811/ DOI: 10.1097/01.fpc.0000230416.82349.90","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Plasma simvastatin lactone and active simvastatin acid","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8f325b66-c640-5772-9b15-68c1500fd16b","evidence_kind":"source_excerpt","locator":"Lines 57-66","start_line":57,"end_line":66,"excerpt":"## slco1b1-c521cc-raises-simvastatin-acid-exposure\nVolunteers with the SLCO1B1 c.521CC genotype had 221 percent greater plasma exposure to active simvastatin acid than those with the c.521TT genotype.\nModel/species: 4 volunteers with c.521CC, 12 with c.521TC and 16 with c.521TT\nTissue/system: Plasma simvastatin lactone and active simvastatin acid\nExposure: Single 40 mg oral simvastatin dose\nRoute: Oral\nDuration: Single dose with 12-hour sampling\nLimits: Peak concentration was 200 percent higher and occurred earlier in c.521CC carriers; the four-carrier group is small.\nPrimary reference: SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. (2006). https://pubmed.ncbi.nlm.nih.gov/17108811/ DOI: 10.1097/01.fpc.0000230416.82349.90\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}