{"id":"d31a6a2e-e089-593c-b902-95777e0082ca","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-clozapine-auc","predicate":"increases","statement":"Caffeine coadministration increased mean clozapine AUC by 19% in the crossover experiment.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0ba36ba2-2775-5abd-9fb2-4e5c21ea2252","mechanism_event_label":"Caffeine changed exposure to a drug sharing its metabolic pathway.","subject":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"object":{"id":"fb672618-f677-53ac-bde3-e06fd8e64af3","slug":"clozapine-plasma-exposure","display_name":"Plasma clozapine exposure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0ba36ba2-2775-5abd-9fb2-4e5c21ea2252","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-clozapine-auc-event","event_type":"observed_relationship","label":"Caffeine changed exposure to a drug sharing its metabolic pathway.","description":"Caffeine coadministration increased mean clozapine AUC by 19% in the crossover experiment.","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":"fb672618-f677-53ac-bde3-e06fd8e64af3","slug":"clozapine-plasma-exposure","display_name":"Plasma clozapine exposure","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":""},{"entity":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"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":"12 nonsmoking healthy men; single 12.5 mg clozapine; caffeine 400–1000 mg/day, mean 550.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Small healthy-volunteer study; patient effect size and toxicity cannot be inferred for an individual.","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":"Caffeine changed exposure to a drug sharing its metabolic pathway.","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":"1b0d04eb-1cf8-5c0f-b57d-756d89886052","evidence_kind":"source_excerpt","locator":"Lines 268-274","start_line":268,"end_line":274,"excerpt":"## caf-clozapine-auc\nCaffeine changed exposure to a drug sharing its metabolic pathway.\nCaffeine coadministration increased mean clozapine AUC by 19% in the crossover experiment.\nModel: 12 nonsmoking healthy men; single 12.5 mg clozapine; caffeine 400–1000 mg/day, mean 550.\nLimitations: Small healthy-volunteer study; patient effect size and toxicity cannot be inferred for an individual.\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":"12 nonsmoking healthy men; single 12.5 mg clozapine; caffeine 400–1000 mg/day, mean 550.","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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