{"id":"894fdbcb-afd2-54fb-afd0-0d1937af2cd8","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-fluvoxamine-exposure","predicate":"increases","statement":"Fluvoxamine increased melatonin AUC about 17-fold and peak concentration about 12-fold on average.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"c3d05fcb-feaa-5af1-9eb6-145ec7a6c04c","mechanism_event_label":"Slowing clearance can sharply raise exposure to an unchanged swallowed dose.","subject":{"id":"df26c2cc-f2ee-543e-81ce-7a332fe3b644","slug":"fluvoxamine","display_name":"Fluvoxamine","entity_type_key":"small_molecule"},"object":{"id":"13670e9e-26f8-55e6-acd8-55f937e95b9c","slug":"melatonin-circulating-exposure","display_name":"Circulating melatonin exposure, route and timing specified","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c3d05fcb-feaa-5af1-9eb6-145ec7a6c04c","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-fluvoxamine-exposure-event","event_type":"observed_intervention","label":"Slowing clearance can sharply raise exposure to an unchanged swallowed dose.","description":"Fluvoxamine increased melatonin AUC about 17-fold and peak concentration about 12-fold on average.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0f0bc1f1-d18d-5652-bc1d-98f61f7ab65c","slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"},"role":"coadministered_substrate","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":"metabolic_context","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"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":2,"notes":""},{"entity":{"id":"13670e9e-26f8-55e6-acd8-55f937e95b9c","slug":"melatonin-circulating-exposure","display_name":"Circulating melatonin exposure, route and timing specified","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/melatonin-research/10668847.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0f3c51771fcf28fd453299490bdedee5088501fb2447e3683edd68b93590d544\", \"start_char\": 0, \"end_char\": 1563, \"text_sha256\": \"0f3c51771fcf28fd453299490bdedee5088501fb2447e3683edd68b93590d544\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Single-dose drug interaction study","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"5 mg melatonin with or without 50 mg fluvoxamine","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Very small study; one CYP2D6 poor metabolizer affected fluvoxamine exposure. Increased melatonin exposure is consistent with inhibited elimination, not proof of increased pineal synthesis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Melatonin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Five healthy male volunteers","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Slowing clearance can sharply raise exposure to an unchanged swallowed dose.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[melatonin-p10668847] Increased bioavailability of oral melatonin after fluvoxamine coadministration. (2000). https://pubmed.ncbi.nlm.nih.gov/10668847/ DOI: 10.1067/mcp.2000.104071","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Oral melatonin pharmacokinetics","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"83d79d91-f210-56d7-9257-79e6273fc780","evidence_kind":"source_excerpt","locator":"Lines 695-706","start_line":695,"end_line":706,"excerpt":"### melatonin-fluvoxamine-exposure\nFluvoxamine increased melatonin AUC about 17-fold and peak concentration about 12-fold on average.\nCondition category: normal\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Slowing clearance can sharply raise exposure to an unchanged swallowed dose.\norganism: Five healthy male volunteers\ntissue_or_cell_type: Oral melatonin pharmacokinetics\nexperimental_model: Single-dose drug interaction study\nlimitations: Very small study; one CYP2D6 poor metabolizer affected fluvoxamine exposure. Increased melatonin exposure is consistent with inhibited elimination, not proof of increased pineal synthesis.\nexposure: 5 mg melatonin with or without 50 mg fluvoxamine\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/10668847.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0f3c51771fcf28fd453299490bdedee5088501fb2447e3683edd68b93590d544\", \"start_char\": 0, \"end_char\": 1563, \"text_sha256\": \"0f3c51771fcf28fd453299490bdedee5088501fb2447e3683edd68b93590d544\"}\n[melatonin-p10668847] Increased bioavailability of oral melatonin after fluvoxamine coadministration. (2000). https://pubmed.ncbi.nlm.nih.gov/10668847/ DOI: 10.1067/mcp.2000.104071","model_system":"Single-dose drug interaction study","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [melatonin-p10668847] Increased bioavailability of oral melatonin after fluvoxamine coadministration. (2000). https://pubmed.ncbi.nlm.nih.gov/10668847/ DOI: 10.1067/mcp.2000.104071","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"bab588de-d217-5038-9c8b-b41222eba08b","stable_key":"import-3279ff78-2460-5064-bfc0-3f2987af85a0","title":"Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"ff4f279d263f95a69da8e7e8a6c6318ab6ba1b55254dbbda1bfa9ce437e1db80","revision_id":"0318eef8-ff38-513e-8ffa-458146ca5e77","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}