Evidence map›Paper›PMID 17178259›Full record

ReviewClinical pharmacology and therapeutics2006

Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance.

Pertti J Neuvonen, Mikko Niemi, Janne T Backman

Registry-linked trialAbstract readReview
PubMed Publisher
In one paragraph

Review in Clinical pharmacology and therapeutics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04608474 (Lipid Management in Renal Transplant Recipients), which is not on this map. Cited by 248 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
248citing papers in PubMed, 10 pooled it
49.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04608474 phase4completedstarted 2021, after this paper: background citation

Lipid Management in Renal Transplant Recipients: a Pilot Study Evaluating the Use of a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK-9) Inhibitor Evolocumab.

Ran2021Enrolled81Registered outcomes3Posted comparisons0ConditionsHyperlipidemiasArmsEvolocumab
PMID 15027968PMID 16303007PMID 21393488PMID 19519808PMID 1434899PMID 24552851PMID 21753749PMID 21067804PMID 20415903PMID 19191769PMID 16095503PMID 16581336other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

248 citing papers in PubMed, 10 syntheses or guidelines pooled it, 842 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Genomewide Association Study of Simvastatin Pharmacokinetics.Clinical pharmacology and therapeutics · 2022
    Pooled it
  4. Association Between Vitamin D Supplementation and Statin-Associated Muscle Symptoms: A Systematic Review.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2022
    Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Statin and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2021 · on this map
    Pooled it
  9. Pooled it
  10. Drug-vitamin D interactions: a systematic review of the literature.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2013
    Pooled it
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Trial

188 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Pertti J NeuvonenDepartment of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. pertti.neuvonen@hus.fi
Mikko Niemi
Janne T Backman
University of Helsinki · FIHelsinki University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl-coenzyme A inhibitors (statins), are widely used in the treatment and prevention of atherosclerotic disease. The benefits of statins are well documented. However, lipid-lowering drugs may cause myopathy, even rhabdomyolysis, the risk of which is increased by certain interactions. Simvastatin, lovastatin, and atorvastatin are metabolized by cytochrome P450 (CYP) 3A4 (simvastatin acid is also metabolized by CYP2C8); their plasma concentrations and risk of myotoxicity are greatly increased by strong inhibitors of CYP3A4 (eg, itraconazole and ritonavir). Weak or moderately potent CYP3A4 inhibitors (eg, verapamil and diltiazem) can be used cautiously with small doses of CYP3A4-dependent statins. Cerivastatin is metabolized by CYP2C8 and CYP3A4, and fluvastatin is metabolized by CYP2C9. The exposure to fluvastatin is increased by less than 2-fold by inhibitors of CYP2C9. Pravastatin, rosuvastatin, and pitavastatin are excreted mainly unchanged, and their plasma concentrations are not significantly increased by pure CYP3A4 inhibitors. Cyclosporine (INN, ciclosporin) inhibits CYP3A4, P-glycoprotein (multidrug resistance protein 1), organic anion transporting polypeptide 1B1 (OATP1B1), and some other hepatic uptake transporters. Gemfibrozil and its glucuronide inhibit CYP2C8 and OATP1B1. These effects of cyclosporine and gemfibrozil explain the increased plasma statin concentrations and, together with pharmacodynamic factors, the increased risk of myotoxicity when coadministered with statins. Inhibitors of OATP1B1 may decrease the benefit/risk ratio of statins by interfering with their entry into hepatocytes, the site of action. Lipid-lowering drugs can be involved also in other interactions, including those between enzyme inducers and CYP3A4 substrate statins, as well as those between gemfibrozil and CYP2C8 substrate antidiabetics. Knowledge of the pharmacokinetic and pharmacodynamic properties of lipid-lowering drugs and their interaction mechanisms helps to avoid adverse interactions, without compromising therapeutic benefits.

Indexed as

Drug InteractionsHydroxymethylglutaryl-CoA Reductase InhibitorsArea Under CurveCytochrome P-450 CYP3ACytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemEnzyme InhibitorsHalf-LifeHumansLiverLiver-Specific Organic Anion Transporter 1Organic Anion TransportersCYP3A4 protein, humanCytochrome P-450 CYP3ACytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemEnzyme InhibitorsHydroxymethylglutaryl-CoA Reductase InhibitorsLiver-Specific Organic Anion Transporter 1Organic Anion TransportersSLCO1B1 protein, human

Identifiers

PMID17178259
OpenAlexW2047207059

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.