{"id":"18157e86-109e-57a9-9381-0dd091fc8664","stable_key":"1bbf9d44-8d2b-5b35-8f82-f6876558b0b3:cyclosporine-lowers-cerivastatin-hepatocyte-uptake","predicate":"reduces_hepatocyte_uptake_of","statement":"Uptake of labelled cerivastatin into human hepatocytes from three donors was inhibited by cyclosporin A with Ki values of 0.3 to 0.7 micromolar, against Km values for the uptake itself of 3 to 18 micromolar, so more than 70 per cent of total uptake at therapeutic concentrations was carrier-mediated.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"4a244e6c-4184-5f15-aba4-ed21ce3f41e4","mechanism_event_label":"Uptake of labelled cerivastatin into human hepatocytes from three donors was inhibited by cyclosporin A with Ki values of 0.3 to 0.7 micromolar, against Km values for the uptake itself of 3 to 18 micr","subject":{"id":"b199063a-fae6-5c5c-9cb4-22c10453bbac","slug":"cyclosporine","display_name":"Cyclosporine","entity_type_key":"drug"},"object":{"id":"ade21be6-666e-59a9-8b89-06996f86551f","slug":"cerivastatin","display_name":"Cerivastatin","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"4a244e6c-4184-5f15-aba4-ed21ce3f41e4","stable_key":"1bbf9d44-8d2b-5b35-8f82-f6876558b0b3:cyclosporine-lowers-cerivastatin-hepatocyte-uptake-event","event_type":"biochemical_relationship","label":"Uptake of labelled cerivastatin into human hepatocytes from three donors was inhibited by cyclosporin A with Ki values of 0.3 to 0.7 micromolar, against Km values for the uptake itself of 3 to 18 micr","description":"Hepatocyte interior","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b199063a-fae6-5c5c-9cb4-22c10453bbac","slug":"cyclosporine","display_name":"Cyclosporine","entity_type_key":"drug"},"role":"acting component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ade21be6-666e-59a9-8b89-06996f86551f","slug":"cerivastatin","display_name":"Cerivastatin","entity_type_key":"small_molecule"},"role":"component the finding is about","stoichiometry":null,"state_label":"","sequence_order":1,"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. 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Three donors is a small panel for a kinetic range.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human hepatocytes from three donors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Uptake of labelled cerivastatin into human hepatocytes from three donors was inhibited by cyclosporin A with Ki values of 0.3 to 0.7 micromolar, against Km values for the uptake itself of 3 to 18 micromolar, so more than 70 per cent of total uptake at therapeutic concentrations was carrier-mediated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. 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No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text.","file_path":"","sha256":"499d00555a629cba2271c3888d7e93627949891d565c4c78c843610de2913080","revision_id":"263ee68a-4184-51d0-a977-197d7ddb7a4d","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}