Evidence map›Paper›PMID 31616046›Full record

ReviewThe pharmacogenomics journal2019

Challenges to assess substrate-dependent allelic effects in CYP450 enzymes and the potential clinical implications.

Lauren A Marcath, Amy L Pasternak, Daniel L Hertz

Abstract readReview
PubMed Publisher
In one paragraph

Review in The pharmacogenomics journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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, 2 syntheses or guidelines pooled it.

  1. Guideline
  2. Guideline
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Article
  8. Lack of association of CYP2B6 pharmacogenetics with cyclophosphamide toxicity in patients with cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022
    Article
  9. Review
  10. Article
  11. Review
  12. Frontiers in pharmacology · 2021
    Article
  13. Review
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.

Lauren A MarcathWashington State University College of Pharmacy and Pharmaceutical Sciences, Spokane, WA, USA.ORCID http://orcid.org/0000-0003-3135-9983
Amy L PasternakDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, 48109-1065, USA.
Daniel L HertzDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, 48109-1065, USA. DLHertz@med.umich.edu.ORCID http://orcid.org/0000-0003-0501-1035

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytochrome P450 enzyme variant alleles have shown evidence that functional consequences differ between substrates. A systematic effort has not yet been made to confirm substrate-dependent activity. This review will discuss the challenges of assessing three examples (CYP2C8*3, CYP2D6*10, and CYP2C9*2) where substrate-dependent activity has been hypothesized with differing levels of evidence and their potential clinical implications. Data supports bidirectional substrate-dependent activity for CYP2C8*3. Although some data suggests CYP2D6*10 causes differences in the magnitude of effect across substrates, confirmatory studies are needed. Convincing evidence for CYP2C9*2 was lacking likely due to compensatory CYP450 metabolism or experimental variability. Confirmed substrate-dependent activity has the potential to impact clinical use of pharmacogenomics, and must be taken into consideration to ensure the goal of improving treatment through personalization is met. It is important for the pharmacogenomics community to begin thinking about this important topic and how it can be best accommodated in clinical practice.

Indexed as

AllelesCytochrome P-450 Enzyme SystemGenetic VariationHumansPharmacogeneticsCytochrome P-450 Enzyme System

Identifiers

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.