{"id":"afbfab2b-8672-5531-8346-53f0bfdd4827","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-efavirenz-interaction","predicate":"increases","statement":"After two weeks of dihydrocapsaicin at 10 mg/kg/day the area under the plasma concentration-time curve for efavirenz increased from 8821 to 22347 micrograms per millilitre per hour, time to maximum plasma concentration increased from 2.50 to 3.50 hours and elimination half-life from 3.13 to 3.51 hours, while plasma clearance fell from 6.71 to 2.65 litres per hour per kilogram, and dihydrocapsaicin significantly inhibited the metabolism of efavirenz in rat liver microsomes; the authors conclude the dose should be monitored in patients on efavirenz maintenance therapy.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0798d709-67c7-5eba-b626-bfde18a5cdb1","mechanism_event_label":"Two weeks of the compound left two and a half times as much of an HIV drug in the blood.","subject":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"object":{"id":"7f18305d-0352-535f-accc-a036e51e9dcd","slug":"efavirenz-exposure","display_name":"Plasma exposure to efavirenz measured as area under the curve","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0798d709-67c7-5eba-b626-bfde18a5cdb1","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-efavirenz-interaction-event","event_type":"biochemical_relationship","label":"Two weeks of the compound left two and a half times as much of an HIV drug in the blood.","description":"After two weeks of dihydrocapsaicin at 10 mg/kg/day the area under the plasma concentration-time curve for efavirenz increased from 8821 to 22347 micrograms per millilitre per hour, time to maximum plasma concentration increased from 2.50 to 3.50 hours and elimination half-life from 3.13 to 3.51 hours, while plasma clearance fell from 6.71 to 2.65 litres per hour per kilogram, and dihydrocapsaicin significantly inhibited the metabolism of efavirenz in rat liver microsomes; the authors conclude the dose should be monitored in patients on efavirenz maintenance therapy.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c7578ffe-ae45-57ed-a440-95eb37b760eb","slug":"efavirenz","display_name":"Efavirenz, a first-line antiretroviral","entity_type_key":"drug"},"role":"affected_drug","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"df2f6be7-32ef-59b2-8838-bc4afe74cd10","slug":"rat-liver-microsomes","display_name":"Rat liver microsomes","entity_type_key":"cell_type"},"role":"test_system","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"457a81ba-23bc-5b4e-9b50-69dbd6f3caba","slug":"hepatic-drug-metabolising-enzymes","display_name":"Hepatic drug-metabolising enzyme activity","entity_type_key":"cellular_process"},"role":"inhibited_process","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"7f18305d-0352-535f-accc-a036e51e9dcd","slug":"efavirenz-exposure","display_name":"Plasma exposure to efavirenz measured as area under the curve","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dihydrocapsaicin-research/41286578.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9063b8f1265e2ca00078e7452f81fc480eea4995c88a595cfbd42d245e74f68e\", \"start_char\": 0, \"end_char\": 1538, \"text_sha256\": \"9063b8f1265e2ca00078e7452f81fc480eea4995c88a595cfbd42d245e74f68e\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Twelve Sprague-Dawley rats pretreated for two weeks, with rat liver microsome experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Dihydrocapsaicin 10 mg/kg/day for two weeks before a single oral 56 mg/kg dose of efavirenz","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A named drug interaction with both in vivo and in vitro arms. 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Twelve rats in two groups, and a rat liver microsome system rather than a human one.\nexposure: Dihydrocapsaicin 10 mg/kg/day for two weeks before a single oral 56 mg/kg dose of efavirenz\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/41286578.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9063b8f1265e2ca00078e7452f81fc480eea4995c88a595cfbd42d245e74f68e\", \"start_char\": 0, \"end_char\": 1538, \"text_sha256\": \"9063b8f1265e2ca00078e7452f81fc480eea4995c88a595cfbd42d245e74f68e\"}\n[dhc-p41286578] Impact of Dihydrocapsaicin on the Metabolism of Efavirenz In Vitro and In Vivo. 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