Atorvastatin

duration

16 weeks

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

84 Japanese type 2 diabetic patients with hypercholesterolaemia

exposure

Atorvastatin for 16 weeks

limitations

An inflammatory marker falling alongside cholesterol in an open-label study does not separate an effect on inflammation from an effect of lower lipids.

organism

84 Japanese type 2 diabetic patients with hypercholesterolaemia

plain_language

Atorvastatin significantly reduced high-sensitivity C-reactive protein alongside the reduction in cholesterol.

primary_references

Atorvastatin lowers plasma low-density lipoprotein cholesterol and C-reactive protein in Japanese type 2 diabetic patients. (2006). https://pubmed.ncbi.nlm.nih.gov/16324921/ DOI: 10.1016/j.metabol.2005.07.017

route

Oral

tissue

High-sensitivity C-reactive protein, with plasminogen activator inhibitor 1, monocyte chemotactic protein 1 and interleukin 6 also measured

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 45–54

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

## atorvastatin-c-reactive-protein Atorvastatin significantly reduced high-sensitivity C-reactive protein alongside the reduction in cholesterol. Model/species: 84 Japanese type 2 diabetic patients with hypercholesterolaemia Tissue/system: High-sensitivity C-reactive protein, with plasminogen activator inhibitor 1, monocyte chemotactic protein 1 and interleukin 6 also measured Exposure: Atorvastatin for 16 weeks Route: Oral Duration: 16 weeks Limits: An inflammatory marker falling alongside cholesterol in an open-label study does not separate an effect on inflammation from an effect of lower lipids. Primary reference: Atorvastatin lowers plasma low-density lipoprotein cholesterol and C-reactive protein in Japanese type 2 diabetic patients. (2006). https://pubmed.ncbi.nlm.nih.gov/16324921/ DOI: 10.1016/j.metabol.2005.07.017 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not applicable

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins

exposure

Statin-enzyme complexes, inhibition constants in the nanomolar range

limitations

The abstract reports structures with six statins without naming them, so this is a class binding mode rather than an atorvastatin-specific structure. Several catalytically relevant residues near the carboxyl terminus are disordered in the complexes.

organism

Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins

plain_language

Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.

primary_references

Structural mechanism for statin inhibition of HMG-CoA reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11349148/ DOI: 10.1126/science.1059344

route

Structural

tissue

Enzyme active-site occupancy

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 13–22

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

## atorvastatin-hmgcr-occupancy Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site. Model/species: Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins Tissue/system: Enzyme active-site occupancy Exposure: Statin-enzyme complexes, inhibition constants in the nanomolar range Route: Structural Duration: Not applicable Limits: The abstract reports structures with six statins without naming them, so this is a class binding mode rather than an atorvastatin-specific structure. Several catalytically relevant residues near the carboxyl terminus are disordered in the complexes. Primary reference: Structural mechanism for statin inhibition of HMG-CoA reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11349148/ DOI: 10.1126/science.1059344 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

16 weeks

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

84 Japanese type 2 diabetic patients with hypercholesterolaemia

exposure

Atorvastatin for 16 weeks, multicentre open-label

limitations

Open-label and without a placebo arm, and responders were defined by reaching an LDL target rather than randomised.

organism

84 Japanese type 2 diabetic patients with hypercholesterolaemia

plain_language

Sixteen weeks of atorvastatin reduced total cholesterol and low-density-lipoprotein cholesterol in type 2 diabetic patients with hypercholesterolaemia.

primary_references

Atorvastatin lowers plasma low-density lipoprotein cholesterol and C-reactive protein in Japanese type 2 diabetic patients. (2006). https://pubmed.ncbi.nlm.nih.gov/16324921/ DOI: 10.1016/j.metabol.2005.07.017

route

Oral

tissue

Plasma lipids

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 34–43

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

## atorvastatin-ldl-cholesterol Sixteen weeks of atorvastatin reduced total cholesterol and low-density-lipoprotein cholesterol in type 2 diabetic patients with hypercholesterolaemia. Model/species: 84 Japanese type 2 diabetic patients with hypercholesterolaemia Tissue/system: Plasma lipids Exposure: Atorvastatin for 16 weeks, multicentre open-label Route: Oral Duration: 16 weeks Limits: Open-label and without a placebo arm, and responders were defined by reaching an LDL target rather than randomised. Primary reference: Atorvastatin lowers plasma low-density lipoprotein cholesterol and C-reactive protein in Japanese type 2 diabetic patients. (2006). https://pubmed.ncbi.nlm.nih.gov/16324921/ DOI: 10.1016/j.metabol.2005.07.017 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Crossover phases, length not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

19 Japanese patients with heterozygous familial hypercholesterolaemia

exposure

Atorvastatin 20 mg or pitavastatin 4 mg, open randomised four-phase crossover

limitations

Pitavastatin lowered coenzyme Q10 by 7.7 percent without reaching significance, so this is a difference in degree; no adverse events or liver or muscle enzyme abnormalities were observed with either statin, and the authors state it remains to be seen whether the change relates to long-term safety.

organism

19 Japanese patients with heterozygous familial hypercholesterolaemia

plain_language

Atorvastatin 20 mg reduced plasma coenzyme Q10 by 26.1 percent, while pitavastatin 4 mg did not, despite comparable reductions in cholesterol.

primary_references

Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia. (2008). https://pubmed.ncbi.nlm.nih.gov/17957184/ DOI: 10.1038/sj.clpt.6100396

route

Oral

tissue

Plasma coenzyme Q10

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 166–175

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

## atorvastatin-lowers-plasma-coenzyme-q10 Atorvastatin 20 mg reduced plasma coenzyme Q10 by 26.1 percent, while pitavastatin 4 mg did not, despite comparable reductions in cholesterol. Model/species: 19 Japanese patients with heterozygous familial hypercholesterolaemia Tissue/system: Plasma coenzyme Q10 Exposure: Atorvastatin 20 mg or pitavastatin 4 mg, open randomised four-phase crossover Route: Oral Duration: Crossover phases, length not stated here Limits: Pitavastatin lowered coenzyme Q10 by 7.7 percent without reaching significance, so this is a difference in degree; no adverse events or liver or muscle enzyme abnormalities were observed with either statin, and the authors state it remains to be seen whether the change relates to long-term safety. Primary reference: Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia. (2008). https://pubmed.ncbi.nlm.nih.gov/17957184/ DOI: 10.1038/sj.clpt.6100396 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

8 weeks

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo

exposure

Simvastatin 80 mg/d or atorvastatin 40 mg/d for 8 weeks

limitations

Endogenous cholesterol synthesis fell by 66 percent in both statin groups, so the muscle result is not explained by weaker target engagement; the simvastatin fall was from 39.7 to 26.4 nmol/g.

organism

48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo

plain_language

Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.

primary_references

High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006

route

Oral

tissue

Skeletal muscle ubiquinone measured in biopsy specimens

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 177–186

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

## atorvastatin-muscle-ubiquinone-null Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms. Model/species: 48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo Tissue/system: Skeletal muscle ubiquinone measured in biopsy specimens Exposure: Simvastatin 80 mg/d or atorvastatin 40 mg/d for 8 weeks Route: Oral Duration: 8 weeks Limits: Endogenous cholesterol synthesis fell by 66 percent in both statin groups, so the muscle result is not explained by weaker target engagement; the simvastatin fall was from 39.7 to 26.4 nmol/g. Primary reference: High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Murine C2C12 myoblasts

exposure

Atorvastatin at IC50, alongside simvastatin and methyl-beta-cyclodextrin

limitations

An IC50 exposure in a proliferating myoblast line is not a therapeutic muscle concentration in a person.

organism

Murine C2C12 myoblasts

plain_language

Atorvastatin at its half-maximal inhibitory concentration reduced the viability of proliferating murine C2C12 myoblasts.

primary_references

Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoskeletal Stabilization. (2018). https://pubmed.ncbi.nlm.nih.gov/29951166/ DOI: 10.1155/2018/6463807

route

In vitro

tissue

Muscle cell viability and regeneration in vitro

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 111–120

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

## atorvastatin-reduces-myoblast-viability Atorvastatin at its half-maximal inhibitory concentration reduced the viability of proliferating murine C2C12 myoblasts. Model/species: Murine C2C12 myoblasts Tissue/system: Muscle cell viability and regeneration in vitro Exposure: Atorvastatin at IC50, alongside simvastatin and methyl-beta-cyclodextrin Route: In vitro Duration: Not stated here Limits: An IC50 exposure in a proliferating myoblast line is not a therapeutic muscle concentration in a person. Primary reference: Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoskeletal Stabilization. (2018). https://pubmed.ncbi.nlm.nih.gov/29951166/ DOI: 10.1155/2018/6463807 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

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.

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.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Murine C2C12 myoblasts

exposure

Geranylgeraniol, farnesol, mevalonate or water-soluble cholesterol co-treatment with statin

limitations

Cholesterol rescued only methyl-beta-cyclodextrin toxicity, and geranylgeranyltransferase inhibition with GGTI-286 could not be reversed by geranylgeraniol, so the rescue requires the transferase to be intact.

organism

Murine C2C12 myoblasts

plain_language

Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.

primary_references

Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoskeletal Stabilization. (2018). https://pubmed.ncbi.nlm.nih.gov/29951166/ DOI: 10.1155/2018/6463807

route

In vitro

tissue

Prenylation of RAP1 and muscle cell viability

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 122–131

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

## geranylgeraniol-rescues-statin-myotoxicity Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1. Model/species: Murine C2C12 myoblasts Tissue/system: Prenylation of RAP1 and muscle cell viability Exposure: Geranylgeraniol, farnesol, mevalonate or water-soluble cholesterol co-treatment with statin Route: In vitro Duration: Not stated here Limits: Cholesterol rescued only methyl-beta-cyclodextrin toxicity, and geranylgeranyltransferase inhibition with GGTI-286 could not be reversed by geranylgeraniol, so the rescue requires the transferase to be intact. Primary reference: Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoskeletal Stabilization. (2018). https://pubmed.ncbi.nlm.nih.gov/29951166/ DOI: 10.1155/2018/6463807 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/coq10-research/16003294.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b", "start_char": 0, "end_char": 1774, "text_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b"}

experimental_model

Randomized double-blind placebo-controlled trial with muscle biopsies

exposure

Simvastatin 80 mg/day, atorvastatin 40 mg/day or placebo for eight weeks

limitations

Different statin/dose regimens. Respiratory-enzyme comparison selected six simvastatin participants with marked CoQ decline and matched participants; not an unbiased whole-arm estimate.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

48 hypercholesterolemic adults in three groups

plain_language

Some regimens lowered the muscle pool, but the finding did not apply equally to every statin arm.

primary_references

[coq10-p16003294] High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006

tissue_or_cell_type

Muscle CoQ and respiratory enzymes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 957–968

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial with muscle biopsies · source_derived_draft · unverified_draft

### coq10-statin-muscle-low Muscle CoQ fell from 39.7 to 26.4 nmol/g with simvastatin 80 mg/day; it did not fall with atorvastatin 40 mg/day or placebo. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some regimens lowered the muscle pool, but the finding did not apply equally to every statin arm. organism: 48 hypercholesterolemic adults in three groups tissue_or_cell_type: Muscle CoQ and respiratory enzymes experimental_model: Randomized double-blind placebo-controlled trial with muscle biopsies limitations: Different statin/dose regimens. Respiratory-enzyme comparison selected six simvastatin participants with marked CoQ decline and matched participants; not an unbiased whole-arm estimate. exposure: Simvastatin 80 mg/day, atorvastatin 40 mg/day or placebo for eight weeks evidence_span: {"source_cache": "artifacts/coq10-research/16003294.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b", "start_char": 0, "end_char": 1774, "text_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b"} [coq10-p16003294] High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006

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.

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.

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.

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

The same 32 healthy volunteers

exposure

Single 10 mg oral rosuvastatin dose, one week apart from the atorvastatin dose

limitations

A within-study comparison of two statins at different doses, so the ratio of effects is not a dose-matched comparison.

organism

The same 32 healthy volunteers

plain_language

The same SLCO1B1 c.521CC genotype raised rosuvastatin exposure by 65 percent, a smaller effect than on atorvastatin, which the authors describe as unexpected for the more hydrophilic statin.

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 rosuvastatin area under the concentration-time curve and peak concentration

OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 46–55

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-rosuvastatin-exposure-less The same SLCO1B1 c.521CC genotype raised rosuvastatin exposure by 65 percent, a smaller effect than on atorvastatin, which the authors describe as unexpected for the more hydrophilic statin. Model/species: The same 32 healthy volunteers Tissue/system: Plasma rosuvastatin area under the concentration-time curve and peak concentration Exposure: Single 10 mg oral rosuvastatin dose, one week apart from the atorvastatin dose Route: Oral Duration: Single dose with 48-hour sampling Limits: A within-study comparison of two statins at different doses, so the ratio of effects is not a dose-matched 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.