{"id":"65f37893-454e-50da-9279-c421d6cef9b3","stable_key":"53d9b98d-e3a0-5416-bc88-adbe42a8cb1b:curcumin-midazolam-null","predicate":"did_not_meaningfully_change","statement":"No meaningful overall midazolam pharmacokinetic change was found.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f24dfabb-28b4-546e-ad37-5f60ef944f2c","mechanism_event_label":"The CYP3A probe did not show the expected major exposure change.","subject":{"id":"749f21cd-de0d-5c92-9bb5-04f9c58b5e1b","slug":"curcuminoid-piperine-preparation","display_name":"Curcuminoid-piperine preparation, study-specific","entity_type_key":"chemical_species"},"object":{"id":"ae3fd583-9887-52f9-9508-d9c1af3e2f2d","slug":"midazolam-plasma-exposure","display_name":"Plasma midazolam exposure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f24dfabb-28b4-546e-ad37-5f60ef944f2c","stable_key":"53d9b98d-e3a0-5416-bc88-adbe42a8cb1b:curcumin-midazolam-null-event","event_type":"observed_intervention","label":"The CYP3A probe did not show the expected major exposure change.","description":"No meaningful overall midazolam pharmacokinetic change was found.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4d9e7b2e-8a2e-59e2-b3e1-35d8155334d5","slug":"midazolam","display_name":"Midazolam","entity_type_key":"small_molecule"},"role":"measured_or_affected_substance","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"749f21cd-de0d-5c92-9bb5-04f9c58b5e1b","slug":"curcuminoid-piperine-preparation","display_name":"Curcuminoid-piperine preparation, study-specific","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ae3fd583-9887-52f9-9508-d9c1af3e2f2d","slug":"midazolam-plasma-exposure","display_name":"Plasma midazolam exposure","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/curcumin-research/22725836.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"255db8a54957c442fe6fca1d21aafe393e3a5506bec7330b49e1bb6f85d86127\", \"start_char\": 0, \"end_char\": 1977, \"text_sha256\": \"255db8a54957c442fe6fca1d21aafe393e3a5506bec7330b49e1bb6f85d86127\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomized six-way crossover in eight healthy volunteers","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"4 g curcuminoids plus 24 mg piperine, four doses over two days before each probe drug","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Short regimen and small sample. A null result for these probes does not establish no interactions with all medicines or preparations.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Curcumin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"curcumin","display_name":"Curcumin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The CYP3A probe did not show the expected major exposure change.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[curcumin-p22725836] Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/22725836/ DOI: 10.1111/j.1365-2125.2012.04364.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Drug pharmacokinetics","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c665c458-ae7f-59d0-b835-21ebe0411692","evidence_kind":"source_excerpt","locator":"Lines 918-929","start_line":918,"end_line":929,"excerpt":"### curcumin-midazolam-null\nNo meaningful overall midazolam pharmacokinetic change was found.\nCondition category: normal\nnutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The CYP3A probe did not show the expected major exposure change.\norganism: Homo sapiens\ntissue_or_cell_type: Drug pharmacokinetics\nexperimental_model: Randomized six-way crossover in eight healthy volunteers\nlimitations: Short regimen and small sample. A null result for these probes does not establish no interactions with all medicines or preparations.\nexposure: 4 g curcuminoids plus 24 mg piperine, four doses over two days before each probe drug\nevidence_span: {\"source_cache\": \"artifacts/curcumin-research/22725836.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"255db8a54957c442fe6fca1d21aafe393e3a5506bec7330b49e1bb6f85d86127\", \"start_char\": 0, \"end_char\": 1977, \"text_sha256\": \"255db8a54957c442fe6fca1d21aafe393e3a5506bec7330b49e1bb6f85d86127\"}\n[curcumin-p22725836] Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. 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