Component

Human cytochrome P450 2C8

Human cytochrome P450 2C8. Species, exposure and limitations are retained in each linked claim.

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. CYP2C8 made a substantial contribution to olanzapine N-demethylation in the tested assays.

    Human cytochrome P450 2C8 → N-Desmethylolanzapine source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"}
    experimental_model
    Human liver microsomes and recombinant enzyme phenotyping
    exposure
    Metabolite-specific assays including albumin effects
    limitations
    In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone.
    nutrient_topic
    Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
    organism
    Human CYP, FMO and UGT enzymes
    plain_language
    This independently identified route also contributes to olanzapine handling.
    primary_references
    [dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
    tissue_or_cell_type
    Olanzapine oxidation and conjugation

    Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 740–751

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver microsomes and recombinant enzyme phenotyping · source_derived_draft · unverified_draft

    ### dim-olanzapine-2c8 CYP2C8 made a substantial contribution to olanzapine N-demethylation in the tested assays. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified route also contributes to olanzapine handling. organism: Human CYP, FMO and UGT enzymes tissue_or_cell_type: Olanzapine oxidation and conjugation experimental_model: Human liver microsomes and recombinant enzyme phenotyping limitations: In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone. exposure: Metabolite-specific assays including albumin effects evidence_span: {"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"} [dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
    Complete structured claim and evidence

  2. Complementary-DNA-expressed CYP2C9 favoured formation of S-2- and S-3-hydroxyibuprofen while CYP2C8 favoured R-2-hydroxyibuprofen formation, high-affinity Km values for S-ibuprofen hydroxylation were 38 and 21 micromolar against 47 and 29 micromolar for R-ibuprofen, sulfaphenazole competitively inhibited all four hydroxylations with submicromolar Ki values, and the regio- and stereoselectivities observed in vitro were consistent with those noted in vivo.

    Human cytochrome P450 2C8 → R(-)-ibuprofen source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ibuprofen-research/9296349.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19179a5f8220c1d4037113812f8968e2730ecf07c6ad94997d2661d7c6c75afb", "start_char": 0, "end_char": 2012, "text_sha256": "19179a5f8220c1d4037113812f8968e2730ecf07c6ad94997d2661d7c6c75afb"}
    experimental_model
    Human liver microsomes and complementary-DNA-expressed cytochromes with a bank of fourteen microsomal preparations
    exposure
    Both enantiomers of ibuprofen assayed for 2- and 3-hydroxylation, with sulfaphenazole, retinol and arachidonic acid as inhibitors
    limitations
    Assigns each enantiomer to a different cytochrome by direct comparison in the same system. In vitro microsomes, though the authors note the selectivities matched those seen in vivo.
    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
    The body uses two different clearance enzymes for the two hands of the same molecule.
    primary_references
    [ibu-p9296349] Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. (1997). https://pubmed.ncbi.nlm.nih.gov/9296349/ DOI: 10.1016/s0006-2952(97)00143-3
    tissue_or_cell_type
    Liver microsomes

    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 201–212

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver microsomes and complementary-DNA-expressed cytochromes with a bank of fourteen microsomal preparations · source_derived_draft · unverified_draft

    ### ibu-different-cytochromes Complementary-DNA-expressed CYP2C9 favoured formation of S-2- and S-3-hydroxyibuprofen while CYP2C8 favoured R-2-hydroxyibuprofen formation, high-affinity Km values for S-ibuprofen hydroxylation were 38 and 21 micromolar against 47 and 29 micromolar for R-ibuprofen, sulfaphenazole competitively inhibited all four hydroxylations with submicromolar Ki values, and the regio- and stereoselectivities observed in vitro were consistent with those noted in vivo. 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: The body uses two different clearance enzymes for the two hands of the same molecule. organism: Human tissue_or_cell_type: Liver microsomes experimental_model: Human liver microsomes and complementary-DNA-expressed cytochromes with a bank of fourteen microsomal preparations limitations: Assigns each enantiomer to a different cytochrome by direct comparison in the same system. In vitro microsomes, though the authors note the selectivities matched those seen in vivo. exposure: Both enantiomers of ibuprofen assayed for 2- and 3-hydroxylation, with sulfaphenazole, retinol and arachidonic acid as inhibitors evidence_span: {"source_cache": "artifacts/ibuprofen-research/9296349.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19179a5f8220c1d4037113812f8968e2730ecf07c6ad94997d2661d7c6c75afb", "start_char": 0, "end_char": 2012, "text_sha256": "19179a5f8220c1d4037113812f8968e2730ecf07c6ad94997d2661d7c6c75afb"} [ibu-p9296349] Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. (1997). https://pubmed.ncbi.nlm.nih.gov/9296349/ DOI: 10.1016/s0006-2952(97)00143-3
    Complete structured claim and evidence

What acts on it

  1. Geraldol reversibly and noncompetitively inhibited CYP2C8-mediated paclitaxel hydroxylation in human liver microsomes, with reported Ki 11.5 micromolar.

    Geraldol / 3-prime-O-methylfisetin → Human cytochrome P450 2C8 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Pooled human liver microsomes; preincubation and kinetic comparisons.
    limitations
    In vitro hazard signal; no measured clinical drug-exposure change or dosing adjustment follows.
    nutrient_topic
    Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
    plain_language
    The parent and metabolite can affect the same drug-metabolizing enzyme.
    primary_references
    Selective inhibition of CYP2C8 by fisetin and its methylated metabolite, geraldol, in human liver microsomes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29454704/ · DOI 10.1016/j.dmpk.2017.12.006

    Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 472–478

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pooled human liver microsomes; preincubation and kinetic comparisons. · source_derived_draft · unverified_draft

    ## fisetin-cyp2c8-metabolite The parent and metabolite can affect the same drug-metabolizing enzyme. Geraldol reversibly and noncompetitively inhibited CYP2C8-mediated paclitaxel hydroxylation in human liver microsomes, with reported Ki 11.5 micromolar. Model: Pooled human liver microsomes; preincubation and kinetic comparisons. Limitations: In vitro hazard signal; no measured clinical drug-exposure change or dosing adjustment follows. Evidence access: Primary abstract Selective inhibition of CYP2C8 by fisetin and its methylated metabolite, geraldol, in human liver microsomes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29454704/ · DOI 10.1016/j.dmpk.2017.12.006
    Complete structured claim and evidence

  2. Fisetin reversibly and noncompetitively inhibited CYP2C8-mediated paclitaxel hydroxylation in human liver microsomes, with reported Ki 4.1 micromolar.

    Fisetin → Human cytochrome P450 2C8 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Pooled human liver microsomes; preincubation and kinetic comparisons.
    limitations
    In vitro hazard signal; no measured clinical drug-exposure change or dosing adjustment follows.
    nutrient_topic
    Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
    plain_language
    The parent and metabolite can affect the same drug-metabolizing enzyme.
    primary_references
    Selective inhibition of CYP2C8 by fisetin and its methylated metabolite, geraldol, in human liver microsomes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29454704/ · DOI 10.1016/j.dmpk.2017.12.006

    Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 464–470

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pooled human liver microsomes; preincubation and kinetic comparisons. · source_derived_draft · unverified_draft

    ## fisetin-cyp2c8-parent The parent and metabolite can affect the same drug-metabolizing enzyme. Fisetin reversibly and noncompetitively inhibited CYP2C8-mediated paclitaxel hydroxylation in human liver microsomes, with reported Ki 4.1 micromolar. Model: Pooled human liver microsomes; preincubation and kinetic comparisons. Limitations: In vitro hazard signal; no measured clinical drug-exposure change or dosing adjustment follows. Evidence access: Primary abstract Selective inhibition of CYP2C8 by fisetin and its methylated metabolite, geraldol, in human liver microsomes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29454704/ · DOI 10.1016/j.dmpk.2017.12.006
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The CYP2C8*3 allele influenced the pharmacokinetics of R-ibuprofen in a gene-dose manner, with plasma half-life after 400 milligrams of 2.0 hours in CYP2C8*1/*1, 4.2 hours in *1/*3 and 9.0 hours in *3/*3 individuals, alongside significant trends in area under the curve and clearance, and the allele frequency of 0.17 in this Spanish Caucasian population was higher than reported elsewhere and was associated with CYP2C9*2 at 2.4-fold the expected frequency.

    The CYP2C8*3 variant allele → R(-)-ibuprofen source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ibuprofen-research/15606441.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "60cffa777fc0b9881548e974376299ec7e970c2785586766150896cbf0561af9", "start_char": 0, "end_char": 1795, "text_sha256": "60cffa777fc0b9881548e974376299ec7e970c2785586766150896cbf0561af9"}
    experimental_model
    Genotype screening of 355 Spanish Caucasians with pharmacokinetics in 25 individuals grouped by CYP2C8 genotype
    exposure
    400 milligrams ibuprofen, with R-ibuprofen disposition followed by genotype
    limitations
    A clear gene-dose effect on the enantiomer that CYP2C9 does not handle. One population, and 25 individuals across the genotype groups.
    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
    A common variant makes the R half linger more than four times as long.
    primary_references
    [ibu-p15606441] The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. (2005). https://pubmed.ncbi.nlm.nih.gov/15606441/ DOI: 10.1111/j.1365-2125.2004.02183.x
    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 227–238

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype screening of 355 Spanish Caucasians with pharmacokinetics in 25 individuals grouped by CYP2C8 genotype · source_derived_draft · unverified_draft

    ### ibu-cyp2c8-and-the-r-hand The CYP2C8*3 allele influenced the pharmacokinetics of R-ibuprofen in a gene-dose manner, with plasma half-life after 400 milligrams of 2.0 hours in CYP2C8*1/*1, 4.2 hours in *1/*3 and 9.0 hours in *3/*3 individuals, alongside significant trends in area under the curve and clearance, and the allele frequency of 0.17 in this Spanish Caucasian population was higher than reported elsewhere and was associated with CYP2C9*2 at 2.4-fold the expected frequency. 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: A common variant makes the R half linger more than four times as long. organism: Human tissue_or_cell_type: Plasma experimental_model: Genotype screening of 355 Spanish Caucasians with pharmacokinetics in 25 individuals grouped by CYP2C8 genotype limitations: A clear gene-dose effect on the enantiomer that CYP2C9 does not handle. One population, and 25 individuals across the genotype groups. exposure: 400 milligrams ibuprofen, with R-ibuprofen disposition followed by genotype evidence_span: {"source_cache": "artifacts/ibuprofen-research/15606441.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "60cffa777fc0b9881548e974376299ec7e970c2785586766150896cbf0561af9", "start_char": 0, "end_char": 1795, "text_sha256": "60cffa777fc0b9881548e974376299ec7e970c2785586766150896cbf0561af9"} [ibu-p15606441] The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. (2005). https://pubmed.ncbi.nlm.nih.gov/15606441/ DOI: 10.1111/j.1365-2125.2004.02183.x
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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