{"id":"1ba28d28-a4d6-5a14-841d-5c17b70d731c","stable_key":"0a5134ca-a214-59b8-8017-f89b299ace92:gemfibrozil-raises-simvastatin-acid-exposure","predicate":"increases","statement":"Gemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"d1bc713b-9d72-5e16-a020-660f8a3b928d","mechanism_event_label":"Gemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent.","subject":{"id":"be172818-3b91-5a27-8657-a620397442da","slug":"gemfibrozil","display_name":"Gemfibrozil","entity_type_key":"drug"},"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":"d1bc713b-9d72-5e16-a020-660f8a3b928d","stable_key":"0a5134ca-a214-59b8-8017-f89b299ace92:gemfibrozil-raises-simvastatin-acid-exposure-event","event_type":"observed_relationship","label":"Gemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent.","description":"Gemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"be172818-3b91-5a27-8657-a620397442da","slug":"gemfibrozil","display_name":"Gemfibrozil","entity_type_key":"drug"},"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":"b7de977d-fed9-5b1c-8138-fd951442b067","slug":"simvastatin","display_name":"Simvastatin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"3 days of gemfibrozil, 12 hours of 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":"10 healthy volunteers, double-blind randomised crossover","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Gemfibrozil 600 mg twice daily for 3 days, then a single 40 mg simvastatin dose","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Gemfibrozil did not inhibit CYP3A4 in human liver microsomes, so the interaction is not a CYP3A4 effect; the authors attribute it to inhibition of non-CYP3A4 metabolism of simvastatin acid.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"10 healthy volunteers, double-blind randomised crossover","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Gemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent.","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 lactone and active simvastatin acid","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e610ef8a-7805-5f7e-aeec-f6594912f1cc","evidence_kind":"source_excerpt","locator":"Lines 24-33","start_line":24,"end_line":33,"excerpt":"## gemfibrozil-raises-simvastatin-acid-exposure\nGemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent.\nModel/species: 10 healthy volunteers, double-blind randomised crossover\nTissue/system: Plasma simvastatin lactone and active simvastatin acid\nExposure: Gemfibrozil 600 mg twice daily for 3 days, then a single 40 mg simvastatin dose\nRoute: Oral\nDuration: 3 days of gemfibrozil, 12 hours of sampling\nLimits: Gemfibrozil did not inhibit CYP3A4 in human liver microsomes, so the interaction is not a CYP3A4 effect; the authors attribute it to inhibition of non-CYP3A4 metabolism of simvastatin acid.\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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