{"id":"97e2c201-1f4c-5bd2-8dbd-653f1f7bec02","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:probe-caffeine","predicate":"context_dependent_observation","statement":"In the six-person cocktail study, caffeine AUC ratios after one 200-mg modafinil dose and seven daily doses were 0.95 and 0.88 (Table 4).","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"499ee9be-d535-5296-a6f6-dcae4b489836","mechanism_event_label":"In the six-person cocktail study, caffeine AUC ratios after one 200-mg modafinil dose and seven daily doses were 0.95 and 0.88 (Table 4).","subject":{"id":"624e6a4b-f96d-5d12-8206-30d1e1715c26","slug":"modafinil","display_name":"Modafinil","entity_type_key":"drug"},"object":{"id":"597640c8-f0e0-5d78-996f-f71ac8a689f8","slug":"caffeine-plasma-exposure","display_name":"Plasma caffeine exposure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"499ee9be-d535-5296-a6f6-dcae4b489836","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:probe-caffeine-event","event_type":"experimental_observation","label":"In the six-person cocktail study, caffeine AUC ratios after one 200-mg modafinil dose and seven daily doses were 0.95 and 0.88 (Table 4).","description":"The six-participant human cocktail study compared baseline with one 200-mg dose and seven daily doses. **Table 4** reports the following AUC ratios:\n\n| Probe | Single dose | Seven doses |\n|---|---:|---:|\n| Caffeine | 0.95 | 0.88 |\n| Dextromethorphan | 0.97 | 0.78 |\n| Losartan | 0.96 | 0.97 |\n| Midazolam | 0.97 | 0.65 |\n| Omeprazole | 1.36 | 1.85 |\n\nThese 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":"Modafinil single dose and seven daily doses","sequence_order":0,"notes":""},{"entity":{"id":"597640c8-f0e0-5d78-996f-f71ac8a689f8","slug":"caffeine-plasma-exposure","display_name":"Plasma caffeine exposure","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"mixed","sequence_order":1,"notes":""},{"entity":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","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\": \"Modafinil single dose and seven daily doses\", \"comparator\": \"Baseline without modafinil\", \"endpoint\": \"In the six-person cocktail study, caffeine AUC ratios after one 200-mg modafinil dose and seven daily doses were 0.95 and 0.88 (Table 4).\", \"effect_direction\": \"mixed\", \"combination\": \"single\", \"conditions\": []}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Human repeated-measures pharmacokinetic study, six participants; one 200-mg dose versus seven 200-mg daily doses, each relative to baseline.","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":"In the six-person cocktail study, caffeine AUC ratios after one 200-mg modafinil dose and seven daily doses were 0.95 and 0.88 (Table 4).","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 116-126; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ce8b4101-887b-5d1d-b8ca-24925e87b345","evidence_kind":"source_excerpt","locator":"Lines 116-126","start_line":116,"end_line":126,"excerpt":"The six-participant human cocktail study compared baseline with one 200-mg dose and seven daily doses. **Table 4** reports the following AUC ratios:\n\n| Probe | Single dose | Seven doses |\n|---|---:|---:|\n| Caffeine | 0.95 | 0.88 |\n| Dextromethorphan | 0.97 | 0.78 |\n| Losartan | 0.96 | 0.97 |\n| Midazolam | 0.97 | 0.65 |\n| Omeprazole | 1.36 | 1.85 |\n\nThese 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":"Human repeated-measures pharmacokinetic study, six participants; one 200-mg dose versus seven 200-mg daily doses, each relative to baseline.","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. Not a verbatim quotation from a primary paper.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"17a64928-eaa2-5117-ba4f-52dcbdf9cc9e","stable_key":"import-6660bba2-4fa0-590a-bf52-9803a24bea9f","title":"Modafinil: detailed mechanisms of action (reviewed 3 October 2026)","document_type":"imported_text","citation_label":"Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication.","file_path":"","sha256":"006008cb4cfd183dd3b0846d3abc66c8ebf40cf1b6bd1f0bcdb4f4d937a8e115","revision_id":"c85b3e2e-c18a-59fc-9e79-5c375e64d119","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}