Evidence map›Paper›PMID 21219398›Full record

ReviewBritish journal of clinical pharmacology2011

4β-Hydroxycholesterol, an endogenous marker of CYP3A4/5 activity in humans.

Ulf Diczfalusy, Hanna Nylén, Pontus Elander, Leif Bertilsson

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in British journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
12.2field-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.

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

97 citing papers in PubMed, 196 citations in OpenAlex.

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  6. Serum 4β-hydroxycholesterol increases during fluconazole treatment.European journal of clinical pharmacology · 2021
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37 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

4 authors at 1 institution in 1 country.

Ulf DiczfalusyDepartment of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Stockholm, Sweden. ulf.diczfalusy@karolinska.se
Hanna Nylén
Pontus Elander
Leif Bertilsson
Karolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have proposed that 4β-hydroxycholesterol (4β-OHC) may be used as an endogenous marker of CYP3A activity. The cholesterol metabolite 4β-OHC is formed by CYP3A4. Treatment of patients with strong inducers of CYP3A enzymes, e.g. anti-epileptic drugs, resulted in 10-fold increased concentrations of plasma 4β-OHC, while treatment with CYP3A inhibitors such as ritonavir or itraconazole resulted in decreased plasma concentrations. There was a relationship between the 4β-OHC concentration and the number of active CYP3A5*1 alleles showing that 4β-OHC was not only formed by CYP3A4, but also by CYP3A5. The concentration of 4β-OHC was higher in women than in men, confirming previous studies indicating a gender difference in CYP3A4/5-activity. The rate of elimination of 4β-OHC is slow (half-life 17 days) which results in stable plasma concentrations within individuals, but limits its use to study rapid changes in CYP3A activity. In short-term studies exogenous markers such as midazolam or quinine may be superior, but in long-term studies 4β-OHC is a sensitive marker of CYP3A activity, especially to assess induction but also inhibition. Under conditions where the cholesterol concentration is changing, the ratio of 4β-OHC:cholesterol may be used as an alternative to 4β-OHC itself. The use of an endogenous CYP3A marker has obvious advantages and may be of value both during drug development and for monitoring CYP3A activity in patients.

Indexed as

BiomarkersCytochrome P-450 CYP3AEthnicityGenotypeHumansHydroxycholesterolsPhenotypeSex CharacteristicsBiomarkerscholest-5-ene-3,4-diolCYP3A4 protein, humanCYP3A5 protein, humanCytochrome P-450 CYP3AHydroxycholesterols

Identifiers

PMID21219398
PMCPMC3040538
OpenAlexW1593954768

What OpenQuestion 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 OpenQuestion graph.