Evidence mapPaperPMID 26095142Full record

Trial reportBritish journal of clinical pharmacology2015

The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity.

Janne Hukkanen, Johanna Puurunen, Tuulia Hyötyläinen, Markku J Savolainen, Aimo Ruokonen, Laure Morin-Papunen, Matej Orešič, Terhi Piltonen, Juha S Tapanainen

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 11% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Results of a Doravirine-Atorvastatin Drug-Drug Interaction Study.Antimicrobial agents and chemotherapy · 2017
    Trial
  4. Article
  5. Review
  6. Article
  7. Observational
  8. Article
  9. 4Frontiers in pharmacology · 2020
    Article
  10. Article
  11. Article
  12. Effect of Fenofibrate Medication on Renal Function.Korean journal of family medicine · 2017
    Article
  13. Article
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

9 authors at 3 institutions in 2 countries.

Janne HukkanenResearch Center for Internal Medicine, University of Oulu, Oulu.ORCID http://orcid.org/0000-0003-4981-0525
Johanna PuurunenMedical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulo.
Tuulia HyötyläinenSteno Diabetes Center, Gentofte, Denmark.
Markku J SavolainenResearch Center for Internal Medicine, University of Oulu, Oulu.
Aimo RuokonenDepartment of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu.
Laure Morin-PapunenMedical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulo.
Matej OrešičSteno Diabetes Center, Gentofte, Denmark.
Terhi PiltonenMedical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulo.
Juha S TapanainenMedical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulo.
Oulu University Hospital · FISteno Diabetes Centers · DKUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsAtorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).

methodsIn this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20 mg day(-1) (n = 15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α-epoxycholesterol ratios were used as negative controls.

resultsTreatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference -0.0595, -0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin -0.032, placebo 0.0055, P = 0.020, 95% CI of the difference -0.069, -0.0067). The ratios of 25-hydroxycholesterol and 5α,6α-epoxycholesterol to cholesterol did not change.

conclusionsThe results establish atorvastatin as an inhibitor of CYP3A4 activity. Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including the conditions with altered cholesterol concentrations.

Indexed as

AdultAtorvastatinCholesterolCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsDouble-Blind MethodFemaleHumansHydroxycholesterolsMiddle AgedPolycystic Ovary Syndrome5,6-epoxycholesterolAtorvastatincholest-5-ene-3,4-diolCholesterolCYP3A4 protein, humanCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsHydroxycholesterols25-hydroxycholesterol4β-hydroxycholesterol5α,6α-epoxycholesterolatorvastatindesmosterolpregnane X receptor

Identifiers

PMID26095142
PMCPMC4574832
OpenAlexW1880939427

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.