{"id":"c8b00e40-ae26-5282-aa7e-853d6a8e5771","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:clinical-cyp3a","predicate":"increases_in_recorded_experiment","statement":"Time-dependent reduction in midazolam exposure after repeated modafinil supports CYP3A induction; a probe-based inference is distinct from direct protein abundance.","claim_class":"mechanistic","status":"source_recorded","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0e457d72-6b6c-5cba-964d-36f11c0b6259","mechanism_event_label":"Time-dependent reduction in midazolam exposure after repeated modafinil supports CYP3A induction; a probe-based inference is distinct from direct protein abundance.","subject":{"id":"624e6a4b-f96d-5d12-8206-30d1e1715c26","slug":"modafinil","display_name":"Modafinil","entity_type_key":"drug"},"object":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"0e457d72-6b6c-5cba-964d-36f11c0b6259","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:clinical-cyp3a-event","event_type":"biochemical_relationship","label":"Time-dependent reduction in midazolam exposure after repeated modafinil supports CYP3A induction; a probe-based inference is distinct from direct protein abundance.","description":"These support time-dependent CYP3A induction and CYP2C19 inhibition. The abstract's estimates differ slightly; the draft's approximately 34%/90% changes follow the abstract. **Source discrepancy:** the discussion calls the dextromethorphan interval 0.69–0.88 contained within 0.85–1.20. That statement is mathematically false. Retain the measurement and query the analysis; do not promote it directly to proven CYP2D6 induction or a definite null. [Trial, Table 4 and discussion](https://pmc.ncbi.nlm.nih.gov/articles/PMC5809348/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"624e6a4b-f96d-5d12-8206-30d1e1715c26","slug":"modafinil","display_name":"Modafinil","entity_type_key":"drug"},"role":"tested factor","stoichiometry":null,"state_label":"Seven daily 200-mg modafinil doses","sequence_order":0,"notes":""},{"entity":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"role":"measured outcome","stoichiometry":null,"state_label":"increase","sequence_order":1,"notes":""},{"entity":{"id":"4d9e7b2e-8a2e-59e2-b3e1-35d8155334d5","slug":"midazolam","display_name":"Midazolam","entity_type_key":"small_molecule"},"role":"probe drug","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract and PMC methods, Tables 3/4, results and discussion inspected; numerical inconsistency preserved in evidence-notes.json.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"Seven daily 200-mg modafinil doses\", \"comparator\": \"Baseline without modafinil\", \"endpoint\": \"Time-dependent reduction in midazolam exposure after repeated modafinil supports CYP3A induction; a probe-based inference is distinct from direct protein abundance.\", \"effect_direction\": \"increase\", \"combination\": \"single\", \"conditions\": []}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Six-person clinical phenotyping study; Table 4 midazolam AUC 0.97 single-dose and 0.65 repeated-dose.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Time-dependent reduction in midazolam exposure after repeated modafinil supports CYP3A induction; a probe-based inference is distinct from direct protein abundance.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol. | 2018 | DOI 10.1111/bcp.13478 | PMID 29178272 | https://pmc.ncbi.nlm.nih.gov/articles/PMC5809348/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 126-126; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9f396689-1d26-5bc2-9a6d-b1615dc3d358","evidence_kind":"source_excerpt","locator":"Lines 126-126","start_line":126,"end_line":126,"excerpt":"These support time-dependent CYP3A induction and CYP2C19 inhibition. The abstract's estimates differ slightly; the draft's approximately 34%/90% changes follow the abstract. **Source discrepancy:** the discussion calls the dextromethorphan interval 0.69–0.88 contained within 0.85–1.20. That statement is mathematically false. Retain the measurement and query the analysis; do not promote it directly to proven CYP2D6 induction or a definite null. [Trial, Table 4 and discussion](https://pmc.ncbi.nlm.nih.gov/articles/PMC5809348/)","model_system":"Six-person clinical phenotyping study; Table 4 midazolam AUC 0.97 single-dose and 0.65 repeated-dose.","directness":"reported_statement","verification_status":"source_recorded","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. 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