{"id":"78e6ac0d-6da6-5602-ad5f-d70fd72fd383","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-primidone-uptake","predicate":"competitively_inhibits","statement":"Primidone competitively inhibited biotin uptake in human intestinal brush-border vesicles (Ki 2.25 mmol/L), without inhibiting basolateral biotin transport.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"c43098ad-1f3a-54e4-b110-6e92d8912c40","mechanism_event_label":"The drug competed with biotin at the gut-facing membrane in this experiment.","subject":{"id":"29b17917-d4ae-5b01-83df-8f1ff59fc8b6","slug":"primidone","display_name":"Primidone","entity_type_key":"small_molecule"},"object":{"id":"d25f4daa-5529-568f-b319-7c30e444914b","slug":"cellular-biotin-uptake","display_name":"Cellular biotin uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c43098ad-1f3a-54e4-b110-6e92d8912c40","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-primidone-uptake-event","event_type":"biochemical_relationship","label":"The drug competed with biotin at the gut-facing membrane in this experiment.","description":"Primidone competitively inhibited biotin uptake in human intestinal brush-border vesicles (Ki 2.25 mmol/L), without inhibiting basolateral biotin transport.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"role":"transport substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"29b17917-d4ae-5b01-83df-8f1ff59fc8b6","slug":"primidone","display_name":"Primidone","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d25f4daa-5529-568f-b319-7c30e444914b","slug":"cellular-biotin-uptake","display_name":"Cellular biotin uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/biotin-research/2911998.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"15113710724eaa76fd9bee5cdf7b031ce185b922c826e10d27aa42235a17aeeb\", \"start_char\": 0, \"end_char\": 1045, \"text_sha256\": \"15113710724eaa76fd9bee5cdf7b031ce185b922c826e10d27aa42235a17aeeb\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transport assays in purified human intestinal brush-border and basolateral membrane vesicles","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Carbamazepine or primidone; millimolar inhibitor constants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"These are membrane-assay concentrations. The study does not establish that prescribed doses cause deficiency in every patient.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Biotin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The drug competed with biotin at the gut-facing membrane in this experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b7-p2911998] Biotin transport in the human intestine: inhibition by anticonvulsant drugs. (1989). https://pubmed.ncbi.nlm.nih.gov/2911998/ DOI: 10.1093/ajcn/49.1.127","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestinal membrane vesicles","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"a9fba0cf-e5b9-5c5a-ad75-9b4126266ff7","evidence_kind":"source_excerpt","locator":"Lines 286-297","start_line":286,"end_line":297,"excerpt":"### b7-primidone-uptake\nPrimidone competitively inhibited biotin uptake in human intestinal brush-border vesicles (Ki 2.25 mmol/L), without inhibiting basolateral biotin transport.\nCondition category: machinery_impairment\nnutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The drug competed with biotin at the gut-facing membrane in this experiment.\norganism: Homo sapiens\ntissue_or_cell_type: Intestinal membrane vesicles\nexperimental_model: Transport assays in purified human intestinal brush-border and basolateral membrane vesicles\nlimitations: These are membrane-assay concentrations. The study does not establish that prescribed doses cause deficiency in every patient.\nexposure: Carbamazepine or primidone; millimolar inhibitor constants\nevidence_span: {\"source_cache\": \"artifacts/biotin-research/2911998.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"15113710724eaa76fd9bee5cdf7b031ce185b922c826e10d27aa42235a17aeeb\", \"start_char\": 0, \"end_char\": 1045, \"text_sha256\": \"15113710724eaa76fd9bee5cdf7b031ce185b922c826e10d27aa42235a17aeeb\"}\n[b7-p2911998] Biotin transport in the human intestine: inhibition by anticonvulsant drugs. (1989). https://pubmed.ncbi.nlm.nih.gov/2911998/ DOI: 10.1093/ajcn/49.1.127","model_system":"Transport assays in purified human intestinal brush-border and basolateral membrane vesicles","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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