{"id":"9871c610-2a7d-599f-9e06-dd7a6bf37120","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-cyp1a2-inhibition","predicate":"inhibits","statement":"In human liver microsomes, fluvoxamine inhibited caffeine demethylated-metabolite formation with Ki values of 0.08–0.28 micromolar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"85eb696d-69aa-516d-8211-6a277a94daad","mechanism_event_label":"An enzyme experiment supports the observed clearance interaction.","subject":{"id":"df26c2cc-f2ee-543e-81ce-7a332fe3b644","slug":"fluvoxamine","display_name":"Fluvoxamine","entity_type_key":"small_molecule"},"object":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"85eb696d-69aa-516d-8211-6a277a94daad","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-cyp1a2-inhibition-event","event_type":"observed_relationship","label":"An enzyme experiment supports the observed clearance interaction.","description":"In human liver microsomes, fluvoxamine inhibited caffeine demethylated-metabolite formation with Ki values of 0.08–0.28 micromolar.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"df26c2cc-f2ee-543e-81ce-7a332fe3b644","slug":"fluvoxamine","display_name":"Fluvoxamine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d6247ee9-3808-5dc9-897a-d81b7ad9f9b8","slug":"paraxanthine","display_name":"Paraxanthine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human liver microsomes; metabolite HPLC.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not all three demethylations are exclusively CYP1A2-dependent.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Caffeine collection; salts, coffee, species and coexposure contexts retain their identities.","comparator":null,"unit":null,"notes":"","entity":{"slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"An enzyme experiment supports the observed clearance interaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Fluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9868741/ · DOI 10.1111/j.1600-0773.1998.tb01476.x","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"3c8e32f3-ef78-58aa-a971-645e3203291d","evidence_kind":"source_excerpt","locator":"Lines 212-218","start_line":212,"end_line":218,"excerpt":"## caf-cyp1a2-inhibition\nAn enzyme experiment supports the observed clearance interaction.\nIn human liver microsomes, fluvoxamine inhibited caffeine demethylated-metabolite formation with Ki values of 0.08–0.28 micromolar.\nModel: Human liver microsomes; metabolite HPLC.\nLimitations: Not all three demethylations are exclusively CYP1A2-dependent.\nEvidence access: Primary abstract\nFluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9868741/ · DOI 10.1111/j.1600-0773.1998.tb01476.x","model_system":"Human liver microsomes; metabolite HPLC.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access stated with the claim.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"40a654db-878c-5471-bc6c-88f4f52599c0","stable_key":"import-ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6","title":"Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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