{"id":"ba2949dd-1c51-5525-80e0-8aae0ee30e56","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-brain-accumulation-without-pgp","predicate":"increases","statement":"Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0b61310a-a050-51de-96a0-99b303002aa6","mechanism_event_label":"Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.","subject":{"id":"a72aed4e-253f-55e0-ae19-59b7141bb026","slug":"mouse-mdr1a-deficiency","display_name":"Mouse mdr1a P-glycoprotein deficiency","entity_type_key":"cellular_process"},"object":{"id":"e90e793f-7291-5472-bb80-4aae7620d351","slug":"ivermectin-brain-concentration","display_name":"Ivermectin concentration in brain","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0b61310a-a050-51de-96a0-99b303002aa6","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-brain-accumulation-without-pgp-event","event_type":"observed_relationship","label":"Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.","description":"Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a72aed4e-253f-55e0-ae19-59b7141bb026","slug":"mouse-mdr1a-deficiency","display_name":"Mouse mdr1a P-glycoprotein deficiency","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e90e793f-7291-5472-bb80-4aae7620d351","slug":"ivermectin-brain-concentration","display_name":"Ivermectin concentration in brain","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e20b8847-c6c0-5add-a457-7e51248dbc2b","slug":"selamectin","display_name":"Selamectin","entity_type_key":"drug"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"c6139b52-4140-5622-9e33-1f6c6385265d","slug":"abcb1","display_name":"Human P-glycoprotein / ABCB1 / MDR1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not stated here","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":"mdr1a,b double knockout mice and bcrp knockout mice, against wild type","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ivermectin 0.2 mg/kg and selamectin 12 mg/kg, intravenous, oral and dermal spot-on","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Breast cancer resistance protein knockouts showed no difference, so this margin is specific to P-glycoprotein and not to efflux transport in general.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"mdr1a,b double knockout mice and bcrp knockout mice, against wild type","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19161460/ DOI: 10.1111/j.1365-2885.2008.01007.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vivo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Brain penetration, organ distribution and plasma kinetics","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d5c9db97-eac8-5ff4-b587-d2537fd13125","evidence_kind":"source_excerpt","locator":"Lines 68-77","start_line":68,"end_line":77,"excerpt":"## ivermectin-brain-accumulation-without-pgp\nIvermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.\nModel/species: mdr1a,b double knockout mice and bcrp knockout mice, against wild type\nTissue/system: Brain penetration, organ distribution and plasma kinetics\nExposure: Ivermectin 0.2 mg/kg and selamectin 12 mg/kg, intravenous, oral and dermal spot-on\nRoute: In vivo\nDuration: Not stated here\nLimits: Breast cancer resistance protein knockouts showed no difference, so this margin is specific to P-glycoprotein and not to efflux transport in general.\nPrimary reference: Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19161460/ DOI: 10.1111/j.1365-2885.2008.01007.x\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":"20818ddd-7b37-5226-a24b-7de007e80eb2","stable_key":"import-e0801c92-7fd3-5cb2-82b7-dd82f010f3ed","title":"Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"c7e1e0201cbd222f0c52b7981f078936ed39b617d747821ed6daa584c2b964a7","revision_id":"56746c3e-cdec-5b8f-a191-425de1a0a7ce","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}