{"id":"c31c8522-64fb-5997-ba3a-db32be54cf0b","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:atorvastatin-muscle-ubiquinone-null","predicate":"no_detected_effect_on","statement":"Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"62f65035-649f-52ab-a8ca-6dfa1dcd3cf4","mechanism_event_label":"Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.","subject":{"id":"64f4b2c7-afdf-5b9a-b6f9-015a7aa96eee","slug":"atorvastatin","display_name":"Atorvastatin","entity_type_key":"small_molecule"},"object":{"id":"9c185815-74b8-5542-b236-f302b620c1e8","slug":"coq-muscle-concentration","display_name":"Muscle coenzyme Q10 concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"62f65035-649f-52ab-a8ca-6dfa1dcd3cf4","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:atorvastatin-muscle-ubiquinone-null-event","event_type":"observed_relationship","label":"Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.","description":"Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"64f4b2c7-afdf-5b9a-b6f9-015a7aa96eee","slug":"atorvastatin","display_name":"Atorvastatin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9c185815-74b8-5542-b236-f302b620c1e8","slug":"coq-muscle-concentration","display_name":"Muscle coenzyme Q10 concentration","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":"8 weeks","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":"48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Simvastatin 80 mg/d or atorvastatin 40 mg/d for 8 weeks","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Endogenous cholesterol synthesis fell by 66 percent in both statin groups, so the muscle result is not explained by weaker target engagement; the simvastatin fall was from 39.7 to 26.4 nmol/g.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Skeletal muscle ubiquinone measured in biopsy specimens","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b5a7c5c2-b77b-53de-a90d-ca9a49d2d528","evidence_kind":"source_excerpt","locator":"Lines 177-186","start_line":177,"end_line":186,"excerpt":"## atorvastatin-muscle-ubiquinone-null\nMuscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.\nModel/species: 48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo\nTissue/system: Skeletal muscle ubiquinone measured in biopsy specimens\nExposure: Simvastatin 80 mg/d or atorvastatin 40 mg/d for 8 weeks\nRoute: Oral\nDuration: 8 weeks\nLimits: Endogenous cholesterol synthesis fell by 66 percent in both statin groups, so the muscle result is not explained by weaker target engagement; the simvastatin fall was from 39.7 to 26.4 nmol/g.\nPrimary reference: High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006\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":"a4431d8c-34d7-5db7-9edf-a35f68feba39","stable_key":"import-1fb6218a-60d1-55ea-87fe-07d15d0fc46f","title":"Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"6307f1acf99f90662320328974781ee660348754257b1e1555701ad597edc8e5","revision_id":"447c5978-ba3f-58fe-ac85-664caa72e01b","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}