{"id":"32eb4944-13cb-5566-84d4-7a8e8407c19c","stable_key":"8ccb5461-efe2-5d95-9869-950d7cd50575:tadalafil-augments-the-nitrate-blood-pressure-fall","predicate":"reduces","statement":"After tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"6ae60304-d767-5095-a96a-c0cc1cca6f26","mechanism_event_label":"After tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours.","subject":{"id":"9820ebfe-515d-50cc-9b44-2bd2be220325","slug":"tadalafil","display_name":"Tadalafil","entity_type_key":"drug"},"object":{"id":"9bd74317-39f2-5b8a-8092-313f154a3795","slug":"standing-systolic-blood-pressure","display_name":"Standing systolic blood pressure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6ae60304-d767-5095-a96a-c0cc1cca6f26","stable_key":"8ccb5461-efe2-5d95-9869-950d7cd50575:tadalafil-augments-the-nitrate-blood-pressure-fall-event","event_type":"observed_relationship","label":"After tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours.","description":"After tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9820ebfe-515d-50cc-9b44-2bd2be220325","slug":"tadalafil","display_name":"Tadalafil","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9bd74317-39f2-5b8a-8092-313f154a3795","slug":"standing-systolic-blood-pressure","display_name":"Standing systolic blood pressure","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d1608eea-1f9a-5578-b18b-8324a702dcbb","slug":"nitroglycerin","display_name":"Nitroglycerin","entity_type_key":"drug"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6d2f509b-3a5b-5a38-b3e7-b148581edec9","slug":"cgmp","display_name":"Cyclic guanosine monophosphate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"80623479-3813-550d-9740-703838fdde70","slug":"tadalafil-plasma-exposure","display_name":"Plasma tadalafil exposure","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Measured to 96 hours after the last tadalafil dose","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"150 male subjects, randomised crossover with a 10 to 21 day washout","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Seven consecutive daily doses of tadalafil 20 mg or placebo, then repeated sublingual nitroglycerin 0.4 mg","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A pharmacodynamic interaction study in male volunteers using a fixed 20 mg dose; the time course reported here describes when the interaction was detectable, not a dosing instruction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"150 male subjects, randomised crossover with a 10 to 21 day washout","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"After tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Time course of the interaction between tadalafil and nitrates. (2003). https://pubmed.ncbi.nlm.nih.gov/14642699/ DOI: 10.1016/j.jacc.2003.09.023","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral tadalafil with sublingual nitroglycerin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Standing systolic and diastolic blood pressure after a nitrate","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"87b1c88c-bce5-51d1-8349-1789a518cd73","evidence_kind":"source_excerpt","locator":"Lines 89-98","start_line":89,"end_line":98,"excerpt":"## tadalafil-augments-the-nitrate-blood-pressure-fall\nAfter tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours.\nModel/species: 150 male subjects, randomised crossover with a 10 to 21 day washout\nTissue/system: Standing systolic and diastolic blood pressure after a nitrate\nExposure: Seven consecutive daily doses of tadalafil 20 mg or placebo, then repeated sublingual nitroglycerin 0.4 mg\nRoute: Oral tadalafil with sublingual nitroglycerin\nDuration: Measured to 96 hours after the last tadalafil dose\nLimits: A pharmacodynamic interaction study in male volunteers using a fixed 20 mg dose; the time course reported here describes when the interaction was detectable, not a dosing instruction.\nPrimary reference: Time course of the interaction between tadalafil and nitrates. (2003). https://pubmed.ncbi.nlm.nih.gov/14642699/ DOI: 10.1016/j.jacc.2003.09.023\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"cca24ae7-e036-525c-a440-4cc2e38ccb4d","stable_key":"import-8ccb5461-efe2-5d95-9869-950d7cd50575","title":"Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text.","file_path":"","sha256":"3df8ec8f7114f983e8cae9fbc54912d3ac5b5f962454afea9dd8d4438c94cded","revision_id":"510acdea-65ae-57a6-b743-68e031ff1f05","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}