{"id":"e1d3173c-4d10-5839-b660-20072cbff7f0","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-dim-pk","predicate":"dose_changes","statement":"Mean peak DIM concentrations were 32, 104 and 108 ng/mL after the reported 100, 200 and 300 mg doses, respectively.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ab53a7f1-f0e8-59b0-a993-df30f4e9144f","mechanism_event_label":"Doubling a dose did not reliably double blood exposure.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"6918867f-aec7-5aac-b2dc-3d2560092128","slug":"dim-plasma-exposure","display_name":"Plasma DIM exposure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ab53a7f1-f0e8-59b0-a993-df30f4e9144f","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-dim-pk-event","event_type":"observed_intervention","label":"Doubling a dose did not reliably double blood exposure.","description":"Mean peak DIM concentrations were 32, 104 and 108 ng/mL after the reported 100, 200 and 300 mg doses, respectively.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6918867f-aec7-5aac-b2dc-3d2560092128","slug":"dim-plasma-exposure","display_name":"Plasma DIM exposure","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/18843002.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c6685bdd57ec7598e6a1fbbbe46f4c8708e0a9a700ed19ebbbc5e35a84c3c60c\", \"start_char\": 0, \"end_char\": 1513, \"text_sha256\": \"c6685bdd57ec7598e6a1fbbbe46f4c8708e0a9a700ed19ebbbc5e35a84c3c60c\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Single ascending-dose randomized pharmacokinetic study","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Absorption-enhanced BR-DIM; small dose cohorts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Formulation-specific, small single-dose cohorts; not a universal safe dose, long-term safety threshold or clinical-efficacy study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Healthy nonsmoking drug-free adults","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Doubling a dose did not reliably double blood exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p18843002] Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. (2008). https://pubmed.ncbi.nlm.nih.gov/18843002/ DOI: 10.1158/1055-9965.epi-08-0520","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Plasma DIM","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ebcfceba-5cbc-500d-9769-e8b28d1d659a","evidence_kind":"source_excerpt","locator":"Lines 194-205","start_line":194,"end_line":205,"excerpt":"### dim-dim-pk\nMean peak DIM concentrations were 32, 104 and 108 ng/mL after the reported 100, 200 and 300 mg doses, respectively.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Doubling a dose did not reliably double blood exposure.\norganism: Healthy nonsmoking drug-free adults\ntissue_or_cell_type: Plasma DIM\nexperimental_model: Single ascending-dose randomized pharmacokinetic study\nlimitations: Formulation-specific, small single-dose cohorts; not a universal safe dose, long-term safety threshold or clinical-efficacy study.\nexposure: Absorption-enhanced BR-DIM; small dose cohorts\nevidence_span: {\"source_cache\": \"artifacts/dim-research/18843002.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c6685bdd57ec7598e6a1fbbbe46f4c8708e0a9a700ed19ebbbc5e35a84c3c60c\", \"start_char\": 0, \"end_char\": 1513, \"text_sha256\": \"c6685bdd57ec7598e6a1fbbbe46f4c8708e0a9a700ed19ebbbc5e35a84c3c60c\"}\n[dim-p18843002] Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. 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