{"id":"821ba488-ae39-58c1-92f6-e94a2ab6ab37","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:clarithromycin-raises-atorvastatin-exposure","predicate":"tested_for_interaction_with","statement":"Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4b756b61-d9cb-5399-bc21-49f590a97209","mechanism_event_label":"Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.","subject":{"id":"63f83925-489b-5621-9066-9bc84e48d55a","slug":"clarithromycin","display_name":"Clarithromycin","entity_type_key":"drug"},"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":"4b756b61-d9cb-5399-bc21-49f590a97209","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:clarithromycin-raises-atorvastatin-exposure-event","event_type":"observed_relationship","label":"Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.","description":"Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"63f83925-489b-5621-9066-9bc84e48d55a","slug":"clarithromycin","display_name":"Clarithromycin","entity_type_key":"drug"},"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":"4df69614-d899-5299-a999-e891f6298c10","slug":"cyp3a4-activity","display_name":"Human CYP3A4 activity, probe and compartment specified","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"222f6587-14d7-5110-902a-f390498c3b12","slug":"cyp3a5","display_name":"Human cytochrome P450 3A5","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Two phases separated by at least 14 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":"23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Single oral atorvastatin 20 mg, with and without clarithromycin 500 mg twice daily for 5 days","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A single-dose interaction study in healthy volunteers, and the abstract does not state the size of the exposure change here.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. (2011). https://pubmed.ncbi.nlm.nih.gov/21950641/ DOI: 10.1592/phco.31.10.942","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 acid and atorvastatin lactone","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0fa498ad-03a5-5bef-adc9-54f94ccb55c6","evidence_kind":"source_excerpt","locator":"Lines 155-164","start_line":155,"end_line":164,"excerpt":"## clarithromycin-raises-atorvastatin-exposure\nClarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.\nModel/species: 23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors\nTissue/system: Plasma atorvastatin acid and atorvastatin lactone\nExposure: Single oral atorvastatin 20 mg, with and without clarithromycin 500 mg twice daily for 5 days\nRoute: Oral\nDuration: Two phases separated by at least 14 days\nLimits: A single-dose interaction study in healthy volunteers, and the abstract does not state the size of the exposure change here.\nPrimary reference: Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. (2011). https://pubmed.ncbi.nlm.nih.gov/21950641/ DOI: 10.1592/phco.31.10.942\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}