{"id":"5d396ecc-c3e2-5b02-8008-23130587577f","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-nicotine-not-smoke","predicate":"did_not_change_trial","statement":"Nicotine patches did not significantly change caffeine pharmacokinetics or metabolite formation in the crossover study.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e39ee129-5e02-5ef3-bcca-c723e9bf8e62","mechanism_event_label":"Smoking and nicotine alone are not interchangeable CYP1A2 exposures.","subject":{"id":"22c6c620-aea4-55ec-9c2a-3cbf914b8997","slug":"nicotine","display_name":"Nicotine","entity_type_key":"small_molecule"},"object":{"id":"a7ade0b8-199b-542e-b9be-c8ad2c2b68c1","slug":"caffeine-clearance","display_name":"Caffeine clearance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e39ee129-5e02-5ef3-bcca-c723e9bf8e62","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-nicotine-not-smoke-event","event_type":"observed_intervention","label":"Smoking and nicotine alone are not interchangeable CYP1A2 exposures.","description":"Nicotine patches did not significantly change caffeine pharmacokinetics or metabolite formation in the crossover study.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"role":"phenotyped_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"22c6c620-aea4-55ec-9c2a-3cbf914b8997","slug":"nicotine","display_name":"Nicotine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a7ade0b8-199b-542e-b9be-c8ad2c2b68c1","slug":"caffeine-clearance","display_name":"Caffeine clearance","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/21599724.publisher-preview.txt\", \"locator\": \"Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2a31ba5c71ba785b8fc6cdec21ed2dfa37686cb6d44dbf22616b0ab9b585a940\", \"start_char\": 0, \"end_char\": 537, \"text_sha256\": \"2a31ba5c71ba785b8fc6cdec21ed2dfa37686cb6d44dbf22616b0ab9b585a940\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomized crossover nicotine-patch study; full-text extract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"42 mg/day transdermal nicotine or placebo; caffeine probe on day eight","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Nicotine-only exposure differs from smoke exposure; this short study does not test every tissue or nicotine product.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"12 healthy smokers abstinent from tobacco during study","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Smoking and nicotine alone are not interchangeable CYP1A2 exposures.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p21599724] Effect of nicotine on cytochrome P450 1A2 activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21599724/ DOI: 10.1111/j.1365-2125.2011.04023.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Caffeine-based hepatic CYP1A2 phenotyping","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"07ab4292-ecfe-5a0c-ab57-2e8a800a1c1d","evidence_kind":"source_excerpt","locator":"Lines 857-868","start_line":857,"end_line":868,"excerpt":"### dim-nicotine-not-smoke\nNicotine patches did not significantly change caffeine pharmacokinetics or metabolite formation in the crossover study.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Smoking and nicotine alone are not interchangeable CYP1A2 exposures.\norganism: 12 healthy smokers abstinent from tobacco during study\ntissue_or_cell_type: Caffeine-based hepatic CYP1A2 phenotyping\nexperimental_model: Randomized crossover nicotine-patch study; full-text extract\nlimitations: Nicotine-only exposure differs from smoke exposure; this short study does not test every tissue or nicotine product.\nexposure: 42 mg/day transdermal nicotine or placebo; caffeine probe on day eight\nevidence_span: {\"source_cache\": \"artifacts/dim-research/21599724.publisher-preview.txt\", \"locator\": \"Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2a31ba5c71ba785b8fc6cdec21ed2dfa37686cb6d44dbf22616b0ab9b585a940\", \"start_char\": 0, \"end_char\": 537, \"text_sha256\": \"2a31ba5c71ba785b8fc6cdec21ed2dfa37686cb6d44dbf22616b0ab9b585a940\"}\n[dim-p21599724] Effect of nicotine on cytochrome P450 1A2 activity. 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