{"id":"c3939505-9f9c-512e-b4e6-f18fa630e0b1","stable_key":"0a5134ca-a214-59b8-8017-f89b299ace92:simvastatin-exposure-raises-myopathy","predicate":"increases","statement":"The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"027d3022-27ff-50d6-9a9b-abe4b5b741a7","mechanism_event_label":"The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.","subject":{"id":"3c530768-ff75-596f-9135-4def848bd08a","slug":"simvastatin-plasma-exposure","display_name":"Plasma simvastatin exposure","entity_type_key":"cellular_process"},"object":{"id":"6d822dfd-c22c-594d-9660-a539e8b22759","slug":"statin-muscle-pain","display_name":"Statin-associated muscle pain","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"027d3022-27ff-50d6-9a9b-abe4b5b741a7","stable_key":"0a5134ca-a214-59b8-8017-f89b299ace92:simvastatin-exposure-raises-myopathy-event","event_type":"observed_relationship","label":"The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.","description":"The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3c530768-ff75-596f-9135-4def848bd08a","slug":"simvastatin-plasma-exposure","display_name":"Plasma simvastatin exposure","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6d822dfd-c22c-594d-9660-a539e8b22759","slug":"statin-muscle-pain","display_name":"Statin-associated muscle pain","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"be172818-3b91-5a27-8657-a620397442da","slug":"gemfibrozil","display_name":"Gemfibrozil","entity_type_key":"drug"},"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":"3 days","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":"10 healthy volunteers, with the myopathy association drawn from prior case reports","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Gemfibrozil co-treatment raising simvastatin acid exposure by 185 percent","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is the authors' mechanistic conclusion linking their measured exposure change to a myopathy risk reported elsewhere, not a measurement of muscle injury in these ten volunteers.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"10 healthy volunteers, with the myopathy association drawn from prior case reports","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Plasma concentrations of active simvastatin acid are increased by gemfibrozil. (2000). https://pubmed.ncbi.nlm.nih.gov/10976543/ DOI: 10.1067/mcp.2000.108507","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 acid concentration and muscle injury risk","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b51fddd6-5e74-53d4-b1aa-f915cf44b481","evidence_kind":"source_excerpt","locator":"Lines 35-44","start_line":35,"end_line":44,"excerpt":"## simvastatin-exposure-raises-myopathy\nThe investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.\nModel/species: 10 healthy volunteers, with the myopathy association drawn from prior case reports\nTissue/system: Plasma simvastatin acid concentration and muscle injury risk\nExposure: Gemfibrozil co-treatment raising simvastatin acid exposure by 185 percent\nRoute: Oral\nDuration: 3 days\nLimits: This is the authors' mechanistic conclusion linking their measured exposure change to a myopathy risk reported elsewhere, not a measurement of muscle injury in these ten volunteers.\nPrimary reference: Plasma concentrations of active simvastatin acid are increased by gemfibrozil. (2000). https://pubmed.ncbi.nlm.nih.gov/10976543/ DOI: 10.1067/mcp.2000.108507\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":"6e42a53a-5f31-5a81-87ba-a3edc49aface","stable_key":"import-0a5134ca-a214-59b8-8017-f89b299ace92","title":"Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of three primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Two share a research group with the OATP1B1 collection and are recorded as one line of evidence with it. Study-specific doses, effect sizes and limitations retained. 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