{"id":"df78baa6-7dea-5768-8896-10be7138862c","stable_key":"3238e4f0-8d45-5c72-8624-6e9a8b20527c:ibu-sixty-three-percent-inverts","predicate":"is_converted_to","statement":"A mean of 63 plus or minus 6% of an administered dose of R(-)-ibuprofen was stereospecifically inverted to the S(+) enantiomer in four healthy male subjects, with no measurable inversion of S(+) to R(-), while the kinetics of the individual enantiomers were altered by concurrent administration of the respective optical antipode, likely reflecting an interaction at plasma protein binding sites, and formation of ester glucuronide conjugates stereoselectively favoured the S enantiomer.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"be59e776-123f-5c21-80d4-629fd23e3fce","mechanism_event_label":"Roughly two thirds of the R half turns into the S half, and none of it comes back.","subject":{"id":"07a563b8-3005-5217-9cc9-b76365f062c7","slug":"r-ibuprofen","display_name":"R(-)-ibuprofen","entity_type_key":"small_molecule"},"object":{"id":"04282f17-56c4-54a9-aa33-37bc4c537c87","slug":"s-ibuprofen","display_name":"S(+)-ibuprofen","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"be59e776-123f-5c21-80d4-629fd23e3fce","stable_key":"3238e4f0-8d45-5c72-8624-6e9a8b20527c:ibu-sixty-three-percent-inverts-event","event_type":"observed_intervention","label":"Roughly two thirds of the R half turns into the S half, and none of it comes back.","description":"A mean of 63 plus or minus 6% of an administered dose of R(-)-ibuprofen was stereospecifically inverted to the S(+) enantiomer in four healthy male subjects, with no measurable inversion of S(+) to R(-), while the kinetics of the individual enantiomers were altered by concurrent administration of the respective optical antipode, likely reflecting an interaction at plasma protein binding sites, and formation of ester glucuronide conjugates stereoselectively favoured the S enantiomer.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b429f269-1d01-59f4-881a-868de0849d0d","slug":"ibuprofen","display_name":"Ibuprofen","entity_type_key":"drug"},"role":"administered_racemate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"69dce1aa-1cfe-5ce3-90f5-7332776d8904","slug":"chiral-inversion","display_name":"Metabolic chiral inversion of a 2-arylpropionic acid","entity_type_key":"cellular_process"},"role":"process","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8cc949c2-f6dd-529c-8236-5ae1aa058216","slug":"ester-glucuronide","display_name":"Acyl (ester) glucuronide conjugate","entity_type_key":"small_molecule"},"role":"stereoselective_conjugate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"90ebf099-f2e7-59ec-8477-1c6c2c6cda83","slug":"plasma-protein-binding-ibu","display_name":"Unbound fraction of drug in plasma","entity_type_key":"cellular_process"},"role":"interacting_process","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"07a563b8-3005-5217-9cc9-b76365f062c7","slug":"r-ibuprofen","display_name":"R(-)-ibuprofen","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"04282f17-56c4-54a9-aa33-37bc4c537c87","slug":"s-ibuprofen","display_name":"S(+)-ibuprofen","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ibuprofen-research/4005104.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"81a2d4fb66dca9706eb1bd4119a918b24385de69633f4c4d01692e7c5bd805d1\", \"start_char\": 0, \"end_char\": 945, \"text_sha256\": \"81a2d4fb66dca9706eb1bd4119a918b24385de69633f4c4d01692e7c5bd805d1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Four healthy male subjects given racemic ibuprofen and each enantiomer separately","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"800 milligrams racemic ibuprofen and 400 milligrams of each enantiomer, on separate occasions","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The design that matters: giving each enantiomer alone as well as the racemate is the only way to see the inversion and the interaction between them. Four subjects.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ibuprofen","display_name":"Ibuprofen","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Roughly two thirds of the R half turns into the S half, and none of it comes back.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ibu-p4005104] Stereoselective disposition of ibuprofen enantiomers in man. (1985). https://pubmed.ncbi.nlm.nih.gov/4005104/ DOI: 10.1111/j.1365-2125.1985.tb02694.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Whole body","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"506401cb-3c97-5353-a3bf-1f16d6c5b009","evidence_kind":"source_excerpt","locator":"Lines 71-82","start_line":71,"end_line":82,"excerpt":"### ibu-sixty-three-percent-inverts\nA mean of 63 plus or minus 6% of an administered dose of R(-)-ibuprofen was stereospecifically inverted to the S(+) enantiomer in four healthy male subjects, with no measurable inversion of S(+) to R(-), while the kinetics of the individual enantiomers were altered by concurrent administration of the respective optical antipode, likely reflecting an interaction at plasma protein binding sites, and formation of ester glucuronide conjugates stereoselectively favoured the S enantiomer.\nCondition category: biomarker_context\nnutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.\nplain_language: Roughly two thirds of the R half turns into the S half, and none of it comes back.\norganism: Human\ntissue_or_cell_type: Whole body\nexperimental_model: Four healthy male subjects given racemic ibuprofen and each enantiomer separately\nlimitations: The design that matters: giving each enantiomer alone as well as the racemate is the only way to see the inversion and the interaction between them. Four subjects.\nexposure: 800 milligrams racemic ibuprofen and 400 milligrams of each enantiomer, on separate occasions\nevidence_span: {\"source_cache\": \"artifacts/ibuprofen-research/4005104.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"81a2d4fb66dca9706eb1bd4119a918b24385de69633f4c4d01692e7c5bd805d1\", \"start_char\": 0, \"end_char\": 945, \"text_sha256\": \"81a2d4fb66dca9706eb1bd4119a918b24385de69633f4c4d01692e7c5bd805d1\"}\n[ibu-p4005104] Stereoselective disposition of ibuprofen enantiomers in man. (1985). https://pubmed.ncbi.nlm.nih.gov/4005104/ DOI: 10.1111/j.1365-2125.1985.tb02694.x","model_system":"Four healthy male subjects given racemic ibuprofen and each enantiomer separately","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ibu-p4005104] Stereoselective disposition of ibuprofen enantiomers in man. (1985). https://pubmed.ncbi.nlm.nih.gov/4005104/ DOI: 10.1111/j.1365-2125.1985.tb02694.x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"31c4939d-f520-55c0-973b-224743caf245","stable_key":"import-3238e4f0-8d45-5c72-8624-6e9a8b20527c","title":"Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"cc2b388178f97f5906b66ecbe441fc5c86d51fd645947c5260fb0b4bdb4bcd21","revision_id":"0b4e5c65-05d3-5430-a4cd-8d6a03647dcb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}