{"id":"87d5966d-bc04-59b1-9652-38933481465f","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-first-pass","predicate":"undergoes_extensive_first_pass_limiting","statement":"Approximately 1% of orally administered coumarin reached systemic circulation unchanged in this pilot study.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3e366025-7635-504a-8fb2-6988e4f88d5e","mechanism_event_label":"Absorbed coumarin was largely transformed before circulating unchanged.","subject":{"id":"9fd9b93a-fdfd-5e09-92d3-0495bff41391","slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"},"object":{"id":"528120d6-590e-59c5-aad8-1a3393fe614b","slug":"coumarin-systemic-parent-exposure","display_name":"Systemic exposure to unchanged coumarin","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3e366025-7635-504a-8fb2-6988e4f88d5e","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-first-pass-event","event_type":"biochemical_relationship","label":"Absorbed coumarin was largely transformed before circulating unchanged.","description":"Approximately 1% of orally administered coumarin reached systemic circulation unchanged in this pilot study.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9fd9b93a-fdfd-5e09-92d3-0495bff41391","slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"528120d6-590e-59c5-aad8-1a3393fe614b","slug":"coumarin-systemic-parent-exposure","display_name":"Systemic exposure to unchanged coumarin","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/coumarin-research/7263928.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385\", \"start_char\": 0, \"end_char\": 1084, \"text_sha256\": \"a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Pilot oral, sustained-release and intravenous pharmacokinetic comparison","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Coumarin formulations; full dosing not specified in abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pilot formulation comparison; low parent exposure does not imply poor intestinal absorption.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Coumarin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Absorbed coumarin was largely transformed before circulating unchanged.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[coumarin-p7263928] Pilot study on bioavailability of coumarin and 7-hydroxycoumarin upon peroral administration of coumarin in a sustained-release dosage form. (1981). https://pubmed.ncbi.nlm.nih.gov/7263928/ DOI: 10.1002/j.1552-4604.1981.tb01770.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Whole blood","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"442c5e42-be54-5949-af0d-35e3cc4b38b0","evidence_kind":"source_excerpt","locator":"Lines 644-655","start_line":644,"end_line":655,"excerpt":"### coumarin-first-pass\nApproximately 1% of orally administered coumarin reached systemic circulation unchanged in this pilot study.\nCondition category: normal\nnutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Absorbed coumarin was largely transformed before circulating unchanged.\norganism: Human\ntissue_or_cell_type: Whole blood\nexperimental_model: Pilot oral, sustained-release and intravenous pharmacokinetic comparison\nlimitations: Pilot formulation comparison; low parent exposure does not imply poor intestinal absorption.\nexposure: Coumarin formulations; full dosing not specified in abstract\nevidence_span: {\"source_cache\": \"artifacts/coumarin-research/7263928.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385\", \"start_char\": 0, \"end_char\": 1084, \"text_sha256\": \"a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385\"}\n[coumarin-p7263928] Pilot study on bioavailability of coumarin and 7-hydroxycoumarin upon peroral administration of coumarin in a sustained-release dosage form. 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