Component

Human CYP3A4 activity, probe and compartment specified

Human CYP3A4 activity, probe and compartment specified. 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. Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.

    Human CYP3A4 activity, probe and compartment specified → Plasma atorvastatin exposure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not applicable
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Human liver microsomes and human recombinant CYP3A enzymes
    exposure
    Atorvastatin, enzyme kinetics showing substrate inhibition
    limitations
    The authors conclude the CYP3A5 polymorphism is therefore unlikely to be an important source of between-person variation in atorvastatin disposition.
    organism
    Human liver microsomes and human recombinant CYP3A enzymes
    plain_language
    Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.
    primary_references
    Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. (2008). https://pubmed.ncbi.nlm.nih.gov/18720283/ DOI: 10.1080/00498250802334391
    route
    In vitro
    tissue
    Hepatic oxidative metabolism

    Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 144–153

    Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## cyp3a4-clears-atorvastatin Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5. Model/species: Human liver microsomes and human recombinant CYP3A enzymes Tissue/system: Hepatic oxidative metabolism Exposure: Atorvastatin, enzyme kinetics showing substrate inhibition Route: In vitro Duration: Not applicable Limits: The authors conclude the CYP3A5 polymorphism is therefore unlikely to be an important source of between-person variation in atorvastatin disposition. Primary reference: Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. (2008). https://pubmed.ncbi.nlm.nih.gov/18720283/ DOI: 10.1080/00498250802334391 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

What acts on it

  1. Moringa methanolic and aqueous leaf extracts inhibited CYP3A4-mediated testosterone 6-beta-hydroxylation in mixed-sex human liver microsomes, with reported IC50 values of 0.5 and 2.5 mg/mL.

    Aqueous and methanolic Moringa leaf extracts → Human CYP3A4 activity, probe and compartment specified source_derived_draftungraded
    Experimental context and source evidence
    dose
    Leaf extracts from 0.01 to 10 mg/mL
    duration
    Incubation interval specified in the primary article
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Mixed-sex human liver microsomes
    limitations
    Extract concentrations and microsomal inhibition do not predict a clinical interaction without constituent exposure and intestinal/hepatic concentrations.
    nutrient_topic
    Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera
    organism
    Mixed-sex human liver microsomes
    plain_language
    Moringa methanolic and aqueous leaf extracts inhibited CYP3A4-mediated testosterone 6-beta-hydroxylation in mixed-sex human liver microsomes, with reported IC50 values of 0.5 and 2.5 mg/mL.
    primary_references
    Moringa oleifera leaf extracts inhibit 6beta-hydroxylation of testosterone by CYP3A4. (2008). https://pubmed.ncbi.nlm.nih.gov/19745507/ DOI: 10.3855/jidc.201
    route
    In vitro
    tissue
    CYP3A4 testosterone 6-beta-hydroxylation

    Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 200–209

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Mixed-sex human liver microsomes · source_derived_draft · unverified_draft

    ## moringa-leaf-extract-cyp3a4 Moringa methanolic and aqueous leaf extracts inhibited CYP3A4-mediated testosterone 6-beta-hydroxylation in mixed-sex human liver microsomes, with reported IC50 values of 0.5 and 2.5 mg/mL. Model/species: Mixed-sex human liver microsomes Tissue/system: CYP3A4 testosterone 6-beta-hydroxylation Exposure: Leaf extracts from 0.01 to 10 mg/mL Route: In vitro Duration: Incubation interval specified in the primary article Limits: Extract concentrations and microsomal inhibition do not predict a clinical interaction without constituent exposure and intestinal/hepatic concentrations. Primary reference: Moringa oleifera leaf extracts inhibit 6beta-hydroxylation of testosterone by CYP3A4. (2008). https://pubmed.ncbi.nlm.nih.gov/19745507/ DOI: 10.3855/jidc.201 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  2. Sulforaphane alone did not change CYP3A activity in the cohort overall; a high-baseline subgroup showed increased midazolam exposure.

    Sulforaphane / SFN, stereochemistry specified per study → Human CYP3A4 activity, probe and compartment specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sulforaphane-research/23153560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec", "start_char": 0, "end_char": 1664, "text_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec"}
    experimental_model
    Three-arm randomized crossover trial
    exposure
    Rifampicin 300 mg/day, with or without sulforaphane 450 micromol/day for seven days; sulforaphane alone
    limitations
    Average null result does not exclude individual or other-drug interactions; high-baseline subgroup finding is not a dosing rule.
    nutrient_topic
    Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
    organism
    Human, 24 healthy adults; humanized-PXR mouse parallel study
    plain_language
    An average null and an exploratory subgroup signal must both remain visible.
    primary_references
    [sulforaphane-p23153560] Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. (2013). https://pubmed.ncbi.nlm.nih.gov/23153560/ DOI: 10.1016/j.taap.2012.10.029
    tissue_or_cell_type
    CYP3A phenotyping with midazolam

    Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1269–1280

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-arm randomized crossover trial · source_derived_draft · unverified_draft

    ### sulforaphane-cyp3a4-alone-null Sulforaphane alone did not change CYP3A activity in the cohort overall; a high-baseline subgroup showed increased midazolam exposure. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: An average null and an exploratory subgroup signal must both remain visible. organism: Human, 24 healthy adults; humanized-PXR mouse parallel study tissue_or_cell_type: CYP3A phenotyping with midazolam experimental_model: Three-arm randomized crossover trial limitations: Average null result does not exclude individual or other-drug interactions; high-baseline subgroup finding is not a dosing rule. exposure: Rifampicin 300 mg/day, with or without sulforaphane 450 micromol/day for seven days; sulforaphane alone evidence_span: {"source_cache": "artifacts/sulforaphane-research/23153560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec", "start_char": 0, "end_char": 1664, "text_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec"} [sulforaphane-p23153560] Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. (2013). https://pubmed.ncbi.nlm.nih.gov/23153560/ DOI: 10.1016/j.taap.2012.10.029
    Complete structured claim and evidence

  3. Coadministration did not prevent rifampicin-driven CYP3A induction; rifampicin alone lowered midazolam AUC by 70%.

    Sulforaphane / SFN, stereochemistry specified per study → Human CYP3A4 activity, probe and compartment specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sulforaphane-research/23153560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec", "start_char": 0, "end_char": 1664, "text_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec"}
    experimental_model
    Three-arm randomized crossover trial
    exposure
    Rifampicin 300 mg/day, with or without sulforaphane 450 micromol/day for seven days; sulforaphane alone
    limitations
    Average null result does not exclude individual or other-drug interactions; high-baseline subgroup finding is not a dosing rule.
    nutrient_topic
    Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
    organism
    Human, 24 healthy adults; humanized-PXR mouse parallel study
    plain_language
    The proposed receptor-blocking effect from laboratory work did not carry through in the human trial.
    primary_references
    [sulforaphane-p23153560] Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. (2013). https://pubmed.ncbi.nlm.nih.gov/23153560/ DOI: 10.1016/j.taap.2012.10.029
    tissue_or_cell_type
    CYP3A phenotyping with midazolam

    Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1256–1267

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-arm randomized crossover trial · source_derived_draft · unverified_draft

    ### sulforaphane-cyp3a4-rifampicin-null Coadministration did not prevent rifampicin-driven CYP3A induction; rifampicin alone lowered midazolam AUC by 70%. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The proposed receptor-blocking effect from laboratory work did not carry through in the human trial. organism: Human, 24 healthy adults; humanized-PXR mouse parallel study tissue_or_cell_type: CYP3A phenotyping with midazolam experimental_model: Three-arm randomized crossover trial limitations: Average null result does not exclude individual or other-drug interactions; high-baseline subgroup finding is not a dosing rule. exposure: Rifampicin 300 mg/day, with or without sulforaphane 450 micromol/day for seven days; sulforaphane alone evidence_span: {"source_cache": "artifacts/sulforaphane-research/23153560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec", "start_char": 0, "end_char": 1664, "text_sha256": "e13099fede346485f6e468497ff2a4754fcae4d0203dde7f54fc9643c0599fec"} [sulforaphane-p23153560] Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. (2013). https://pubmed.ncbi.nlm.nih.gov/23153560/ DOI: 10.1016/j.taap.2012.10.029
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.

    Clarithromycin → Plasma atorvastatin exposure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Two phases separated by at least 14 days
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors
    exposure
    Single oral atorvastatin 20 mg, with and without clarithromycin 500 mg twice daily for 5 days
    limitations
    A single-dose interaction study in healthy volunteers, and the abstract does not state the size of the exposure change here.
    organism
    23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors
    plain_language
    Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.
    primary_references
    Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. (2011). https://pubmed.ncbi.nlm.nih.gov/21950641/ DOI: 10.1592/phco.31.10.942
    route
    Oral
    tissue
    Plasma atorvastatin acid and atorvastatin lactone

    Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 155–164

    Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## clarithromycin-raises-atorvastatin-exposure Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5. Model/species: 23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors Tissue/system: Plasma atorvastatin acid and atorvastatin lactone Exposure: Single oral atorvastatin 20 mg, with and without clarithromycin 500 mg twice daily for 5 days Route: Oral Duration: Two phases separated by at least 14 days Limits: A single-dose interaction study in healthy volunteers, and the abstract does not state the size of the exposure change here. Primary reference: Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. (2011). https://pubmed.ncbi.nlm.nih.gov/21950641/ DOI: 10.1592/phco.31.10.942 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    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.

    Evidence, AI assistance and curation standards