Unbound fraction of drug in plasma

Where it participates (unsigned role)

1. After oral administration of 800 milligrams of racemic ibuprofen to six healthy male volunteers the mean time-averaged percentage unbound of the R(-) enantiomer was 0.419, significantly less than that of the S(+) enantiomer at 0.643, consistent with stereoselective plasma protein binding, and the unbound percentage of each enantiomer was concentration-dependent across the therapeutic range and influenced by the presence of its optical antipode.

   R(-)-ibuprofen → S(+)-ibuprofen source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/ibuprofen-research/2744069.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f73cd7aeb524ce11255efc7c629968dc35bafed4049636024dc2598c649ec858", "start_char": 0, "end_char": 905, "text_sha256": "f73cd7aeb524ce11255efc7c629968dc35bafed4049636024dc2598c649ec858"}

   experimental_model

   Equilibrium dialysis with diastereomeric derivatisation and radiochemical analysis in six healthy male volunteers

   exposure

   800 milligrams racemic ibuprofen orally, with each enantiomer measured in the presence of the other

   limitations

   Measures the two enantiomers in the presence of each other, which is the condition that actually obtains after a tablet. Six volunteers.

   nutrient_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. · Ibuprofen

   organism

   Human

   plain_language

   Less of the R form is free in the blood than the S form, and each changes the other.

   primary_references

   [ibu-p2744069] Stereoselective plasma protein binding of ibuprofen enantiomers. (1989). https://pubmed.ncbi.nlm.nih.gov/2744069/ DOI: 10.1007/bf00558161

   tissue_or_cell_type

   Plasma

   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) · lines 188–199

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Equilibrium dialysis with diastereomeric derivatisation and radiochemical analysis in six healthy male volunteers · source_derived_draft · unverified_draft

   ### ibu-binding-differs-between-hands After oral administration of 800 milligrams of racemic ibuprofen to six healthy male volunteers the mean time-averaged percentage unbound of the R(-) enantiomer was 0.419, significantly less than that of the S(+) enantiomer at 0.643, consistent with stereoselective plasma protein binding, and the unbound percentage of each enantiomer was concentration-dependent across the therapeutic range and influenced by the presence of its optical antipode. Condition category: normal nutrient_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. plain_language: Less of the R form is free in the blood than the S form, and each changes the other. organism: Human tissue_or_cell_type: Plasma experimental_model: Equilibrium dialysis with diastereomeric derivatisation and radiochemical analysis in six healthy male volunteers limitations: Measures the two enantiomers in the presence of each other, which is the condition that actually obtains after a tablet. Six volunteers. exposure: 800 milligrams racemic ibuprofen orally, with each enantiomer measured in the presence of the other evidence_span: {"source_cache": "artifacts/ibuprofen-research/2744069.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f73cd7aeb524ce11255efc7c629968dc35bafed4049636024dc2598c649ec858", "start_char": 0, "end_char": 905, "text_sha256": "f73cd7aeb524ce11255efc7c629968dc35bafed4049636024dc2598c649ec858"} [ibu-p2744069] Stereoselective plasma protein binding of ibuprofen enantiomers. (1989). https://pubmed.ncbi.nlm.nih.gov/2744069/ DOI: 10.1007/bf00558161

   Complete structured claim and evidence

2. Measurement of the inhibitory potency of non-steroidal anti-inflammatory drugs on cyclooxygenase isoforms is strongly influenced by variations in experimental conditions, the concentration of protein in the assay medium being particularly important because these drugs are highly protein bound in vivo so that assays based on human whole blood provide the most suitable test system, and of the drugs investigated only meloxicam showed selectivity for cyclooxygenase-2 at therapeutically relevant concentrations while standard drugs such as naproxen inhibited both isoforms to an equal degree.

   The human whole blood assay of cyclooxygenase activity → The ratio of cyclooxygenase-1 to cyclooxygenase-2 inhibitory potency source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/ibuprofen-research/9219317.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3edafe44ec9bf9e15505ffebb96add5467f8874fe8b585ce3878c473f250714", "start_char": 0, "end_char": 1162, "text_sha256": "d3edafe44ec9bf9e15505ffebb96add5467f8874fe8b585ce3878c473f250714"}

   experimental_model

   Comparison of cyclooxygenase inhibitory potency across assay systems, using the human whole blood assay

   exposure

   Standard non-steroidal anti-inflammatory drugs compared at therapeutically relevant concentrations

   limitations

   Argues that the whole blood assay is the appropriate test because these drugs are highly protein bound. It reports conclusions about the class, with naproxen named rather than ibuprofen.

   nutrient_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. · Ibuprofen

   organism

   Human

   plain_language

   Measured in blood rather than in a tube of enzyme, the ordinary anti-inflammatories hit both enzymes about equally.

   primary_references

   [ibu-p9219317] Differentiating among nonsteroidal antiinflammatory drugs by pharmacokinetic and pharmacodynamic profiles. (1997). https://pubmed.ncbi.nlm.nih.gov/9219317/ DOI: 10.1016/s0049-0172(97)80050-9

   tissue_or_cell_type

   Whole blood

   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) · lines 344–355

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparison of cyclooxygenase inhibitory potency across assay systems, using the human whole blood assay · source_derived_draft · unverified_draft

   ### ibu-no-selectivity-in-whole-blood Measurement of the inhibitory potency of non-steroidal anti-inflammatory drugs on cyclooxygenase isoforms is strongly influenced by variations in experimental conditions, the concentration of protein in the assay medium being particularly important because these drugs are highly protein bound in vivo so that assays based on human whole blood provide the most suitable test system, and of the drugs investigated only meloxicam showed selectivity for cyclooxygenase-2 at therapeutically relevant concentrations while standard drugs such as naproxen inhibited both isoforms to an equal degree. Condition category: normal nutrient_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. plain_language: Measured in blood rather than in a tube of enzyme, the ordinary anti-inflammatories hit both enzymes about equally. organism: Human tissue_or_cell_type: Whole blood experimental_model: Comparison of cyclooxygenase inhibitory potency across assay systems, using the human whole blood assay limitations: Argues that the whole blood assay is the appropriate test because these drugs are highly protein bound. It reports conclusions about the class, with naproxen named rather than ibuprofen. exposure: Standard non-steroidal anti-inflammatory drugs compared at therapeutically relevant concentrations evidence_span: {"source_cache": "artifacts/ibuprofen-research/9219317.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3edafe44ec9bf9e15505ffebb96add5467f8874fe8b585ce3878c473f250714", "start_char": 0, "end_char": 1162, "text_sha256": "d3edafe44ec9bf9e15505ffebb96add5467f8874fe8b585ce3878c473f250714"} [ibu-p9219317] Differentiating among nonsteroidal antiinflammatory drugs by pharmacokinetic and pharmacodynamic profiles. (1997). https://pubmed.ncbi.nlm.nih.gov/9219317/ DOI: 10.1016/s0049-0172(97)80050-9

   Complete structured claim and evidence

3. 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.

   R(-)-ibuprofen → S(+)-ibuprofen source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_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"}

   experimental_model

   Four healthy male subjects given racemic ibuprofen and each enantiomer separately

   exposure

   800 milligrams racemic ibuprofen and 400 milligrams of each enantiomer, on separate occasions

   limitations

   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.

   nutrient_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. · Ibuprofen

   organism

   Human

   plain_language

   Roughly two thirds of the R half turns into the S half, and none of it comes back.

   primary_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

   tissue_or_cell_type

   Whole body

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   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) · lines 71–82

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four healthy male subjects given racemic ibuprofen and each enantiomer separately · source_derived_draft · unverified_draft

   ### ibu-sixty-three-percent-inverts 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. Condition category: biomarker_context nutrient_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. plain_language: Roughly two thirds of the R half turns into the S half, and none of it comes back. organism: Human tissue_or_cell_type: Whole body experimental_model: Four healthy male subjects given racemic ibuprofen and each enantiomer separately limitations: 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. exposure: 800 milligrams racemic ibuprofen and 400 milligrams of each enantiomer, on separate occasions evidence_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"} [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

   Complete structured claim and evidence