{"id":"391c83fb-1d63-51c5-84c7-c6974e51038f","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-contraceptive-exposure","predicate":"associated_with_higher","statement":"Melatonin AUC and peak concentrations were about four- to fivefold higher in oral-contraceptive users than nonusers.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"cdf5a428-2862-5f38-b470-6d651e399518","mechanism_event_label":"Medication context changes how a dose appears in the bloodstream.","subject":{"id":"af0b4ecc-049f-50d7-80a6-faa6407df1d2","slug":"oral-contraceptive-mixture","display_name":"Study-specific oral contraceptive formulations","entity_type_key":"chemical_species"},"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":"cdf5a428-2862-5f38-b470-6d651e399518","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-contraceptive-exposure-event","event_type":"observed_intervention","label":"Medication context changes how a dose appears in the bloodstream.","description":"Melatonin AUC and peak concentrations were about four- to fivefold higher in oral-contraceptive users than nonusers.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0f0bc1f1-d18d-5652-bc1d-98f61f7ab65c","slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"},"role":"administered_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":"af0b4ecc-049f-50d7-80a6-faa6407df1d2","slug":"oral-contraceptive-mixture","display_name":"Study-specific oral contraceptive formulations","entity_type_key":"chemical_species"},"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/18490497.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ab9a91b566e88a73ccbd20d9152934f6a048348bc18ec0c2535ec5a9142dc0e4\", \"start_char\": 0, \"end_char\": 927, \"text_sha256\": \"ab9a91b566e88a73ccbd20d9152934f6a048348bc18ec0c2535ec5a9142dc0e4\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Pharmacokinetic comparison by contraceptive use and genotype","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"6 mg melatonin; oral contraceptive users versus nonusers","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Formulations were not universal across all contraceptives. Exposure comparison is not proof all hormone treatments behave identically; genotype effects were nonsignificant.","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":"29 human participants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Medication context changes how a dose appears in the bloodstream.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[melatonin-p18490497] The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C>A polymorphism. (2008). https://pubmed.ncbi.nlm.nih.gov/18490497/ DOI: 10.1177/0091270008318669","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Melatonin clearance","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2ac278fc-e2a5-5adc-975c-4e62638d8a67","evidence_kind":"source_excerpt","locator":"Lines 721-732","start_line":721,"end_line":732,"excerpt":"### melatonin-contraceptive-exposure\nMelatonin AUC and peak concentrations were about four- to fivefold higher in oral-contraceptive users than nonusers.\nCondition category: normal\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Medication context changes how a dose appears in the bloodstream.\norganism: 29 human participants\ntissue_or_cell_type: Melatonin clearance\nexperimental_model: Pharmacokinetic comparison by contraceptive use and genotype\nlimitations: Formulations were not universal across all contraceptives. Exposure comparison is not proof all hormone treatments behave identically; genotype effects were nonsignificant.\nexposure: 6 mg melatonin; oral contraceptive users versus nonusers\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/18490497.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ab9a91b566e88a73ccbd20d9152934f6a048348bc18ec0c2535ec5a9142dc0e4\", \"start_char\": 0, \"end_char\": 927, \"text_sha256\": \"ab9a91b566e88a73ccbd20d9152934f6a048348bc18ec0c2535ec5a9142dc0e4\"}\n[melatonin-p18490497] The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C>A polymorphism. 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