Component

Plasma atorvastatin exposure

Circulating atorvastatin acid and atorvastatin lactone.

6 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 acts on it

  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

  2. 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

  3. OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.

    Human OATP1B1 / SLCO1B1 → Plasma atorvastatin exposure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Single dose in both designs
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype
    exposure
    Rifampicin inhibition in one study and the SLCO1B1 c.521CC genotype in another
    limitations
    This is the mechanistic reading shared by an inhibitor study and a genotype study rather than a single measurement of transporter activity against exposure; neither study measured OATP1B1 activity directly in the participants.
    organism
    Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype
    plain_language
    OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.
    primary_references
    The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038
    route
    Oral atorvastatin
    tissue
    Hepatic sinusoidal uptake and systemic plasma exposure

    OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 24–33

    Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## oatp1b1-activity-lowers-atorvastatin-exposure OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration. Model/species: Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype Tissue/system: Hepatic sinusoidal uptake and systemic plasma exposure Exposure: Rifampicin inhibition in one study and the SLCO1B1 c.521CC genotype in another Route: Oral atorvastatin Duration: Single dose in both designs Limits: This is the mechanistic reading shared by an inhibitor study and a genotype study rather than a single measurement of transporter activity against exposure; neither study measured OATP1B1 activity directly in the participants. Primary reference: The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  4. A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.

    Rifampicin → Plasma atorvastatin exposure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Single dose, sampling to 24 hours
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    11 healthy human volunteers, randomised crossover
    exposure
    Two 40 mg oral atorvastatin doses one week apart, with one 30-minute intravenous infusion of 600 mg rifampicin on one of the two study days
    limitations
    Rifampicin is used here as a model hepatic uptake inhibitor and is not selective for OATP1B1; the lactone forms rose less than the acid, and a single intravenous dose avoids the enzyme induction that repeated oral rifampicin would cause.
    organism
    11 healthy human volunteers, randomised crossover
    plain_language
    A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.
    primary_references
    The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038
    route
    Oral atorvastatin with intravenous rifampicin
    tissue
    Plasma atorvastatin acid and its hydroxy metabolites

    OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 13–22

    Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## rifampicin-raises-atorvastatin-exposure A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers. Model/species: 11 healthy human volunteers, randomised crossover Tissue/system: Plasma atorvastatin acid and its hydroxy metabolites Exposure: Two 40 mg oral atorvastatin doses one week apart, with one 30-minute intravenous infusion of 600 mg rifampicin on one of the two study days Route: Oral atorvastatin with intravenous rifampicin Duration: Single dose, sampling to 24 hours Limits: Rifampicin is used here as a model hepatic uptake inhibitor and is not selective for OATP1B1; the lactone forms rose less than the acid, and a single intravenous dose avoids the enzyme induction that repeated oral rifampicin would cause. Primary reference: The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  5. Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.

    SLCO1B1 c.521T>C reduced-function variant → Plasma atorvastatin exposure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Single dose with 48-hour sampling
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT
    exposure
    Single 20 mg oral atorvastatin dose
    limitations
    Only four participants carried the c.521CC genotype, and 2-hydroxyatorvastatin exposure was 100 percent greater in the same comparison.
    organism
    32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT
    plain_language
    Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.
    primary_references
    Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. (2007). https://pubmed.ncbi.nlm.nih.gov/17473846/ DOI: 10.1038/sj.clpt.6100220
    route
    Oral
    tissue
    Plasma atorvastatin area under the concentration-time curve from 0 to 48 hours

    OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 35–44

    Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## slco1b1-c521cc-raises-atorvastatin-exposure Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype. Model/species: 32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT Tissue/system: Plasma atorvastatin area under the concentration-time curve from 0 to 48 hours Exposure: Single 20 mg oral atorvastatin dose Route: Oral Duration: Single dose with 48-hour sampling Limits: Only four participants carried the c.521CC genotype, and 2-hydroxyatorvastatin exposure was 100 percent greater in the same comparison. Primary reference: Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. (2007). https://pubmed.ncbi.nlm.nih.gov/17473846/ DOI: 10.1038/sj.clpt.6100220 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.

    Human OATP1B1 / SLCO1B1 → Statin-associated muscle pain 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
    Review of human pharmacogenetic and pharmacokinetic studies
    exposure
    SLCO1B1 c.521T>C, protein p.V174A, rs4149056
    limitations
    This is a review statement summarising several studies rather than a single measurement, the effect differs between statins, and it describes the variant's effect on activity rather than a directly measured activity-to-myopathy relationship.
    organism
    Review of human pharmacogenetic and pharmacokinetic studies
    plain_language
    The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.
    primary_references
    Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21245207/ DOI: 10.1124/pr.110.002857
    route
    Oral statins
    tissue
    Hepatic uptake, plasma statin concentration and skeletal muscle injury

    OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 68–77

    Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## oatp1b1-activity-lowers-statin-myopathy-risk The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins. Model/species: Review of human pharmacogenetic and pharmacokinetic studies Tissue/system: Hepatic uptake, plasma statin concentration and skeletal muscle injury Exposure: SLCO1B1 c.521T>C, protein p.V174A, rs4149056 Route: Oral statins Duration: Not applicable Limits: This is a review statement summarising several studies rather than a single measurement, the effect differs between statins, and it describes the variant's effect on activity rather than a directly measured activity-to-myopathy relationship. Primary reference: Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21245207/ DOI: 10.1124/pr.110.002857 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