{"id":"39a973a4-8912-5de6-8186-441e2e5ae207","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-clozapine-clear","predicate":"reduces","statement":"Mean clozapine oral clearance fell 14%; metabolite-to-parent ratios also fell during caffeine exposure.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"5eaafda5-228d-5a9b-8be9-fbb2a726fd0c","mechanism_event_label":"The pharmacokinetic pattern supported reduced drug metabolism.","subject":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"object":{"id":"f623d23b-4de6-5790-9083-8227f1ad3015","slug":"clozapine-oral-clearance","display_name":"Clozapine oral clearance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5eaafda5-228d-5a9b-8be9-fbb2a726fd0c","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-clozapine-clear-event","event_type":"observed_relationship","label":"The pharmacokinetic pattern supported reduced drug metabolism.","description":"Mean clozapine oral clearance fell 14%; metabolite-to-parent ratios also fell during caffeine exposure.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f623d23b-4de6-5790-9083-8227f1ad3015","slug":"clozapine-oral-clearance","display_name":"Clozapine oral clearance","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"2131891d-599e-5f0d-99f2-641cbbae52a7","slug":"clozapine","display_name":"Clozapine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Same randomized open-label crossover.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not a medication-adjustment rule.","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":"The pharmacokinetic pattern supported reduced drug metabolism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10606838/ · DOI 10.1046/j.1365-2125.2000.00111.x","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"af83f026-fade-5c09-a24a-e13aa829cb39","evidence_kind":"source_excerpt","locator":"Lines 276-282","start_line":276,"end_line":282,"excerpt":"## caf-clozapine-clear\nThe pharmacokinetic pattern supported reduced drug metabolism.\nMean clozapine oral clearance fell 14%; metabolite-to-parent ratios also fell during caffeine exposure.\nModel: Same randomized open-label crossover.\nLimitations: Not a medication-adjustment rule.\nEvidence access: Primary abstract\nEffect of caffeine on clozapine pharmacokinetics in healthy volunteers. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10606838/ · DOI 10.1046/j.1365-2125.2000.00111.x","model_system":"Same randomized open-label crossover.","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. Not publisher full text.","file_path":"","sha256":"780d73d4abd45a0284d2cc0c646dbe8432ae347362891a4b98a19a61341a7325","revision_id":"f36ffb0a-d6df-522f-b783-5e30214b9e26","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}