Evidence map›Paper›PMID 40980418›Full record

ReviewDrug design, development and therapy2025

CYP2C8-Mediated Drug-Drug Interactions and the Factors Influencing the Interaction Magnitude.

Ling-Ling Zhu, Ling-Yan Yu, Yan-Hong Wang, Quan Zhou

Abstract readReview
In one paragraph

Review in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
  2. 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

4 authors.

Ling-Ling Zhu *VIP Care and Geriatric Ward, Division of Nursing, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
Ling-Yan Yu *Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
Yan-Hong WangDepartment of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
Quan ZhouDepartment of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.ORCID 0000-0002-3314-0451

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Older adults often have multiple morbidities that may lead to polypharmacy. Cytochrome P450 (CYP) 2C8 has shown significant contributions in the metabolism of various medications; however, its related drug-drug interactions (DDIs) appear to be underrecognized in clinical practice compared to the major CYP enzymes (eg, CYP3A4, CYP2D6). This review summarizes the progress of CYP2C8-mediated DDIs and factors influencing the interaction magnitude. Methods: Using CYP2C8 and drug interactions as the search terms, literature was searched through PubMed, Web of Science, and Embase as of January 2025. Eligible studies were identified following PRISMA guidelines. Screening and inclusion were assessed by two independent reviewers and 57 studies met inclusion/exclusion criteria. Results: Based on authoritative sources (FDA, EMA, DrugBank), and literature, this review identified 5 inducers, 53 strong/moderate inhibitors, and 32 major/intermediate substrates of CYP2C8. Typical examples were illustrated to predict DDIs by in vitro-in vivo extrapolation. The factors influencing DDI magnitude include genetic polymorphisms (CYP2C8, SLCO1B1, UDP-glucuronosyltransferase, and pregnane X receptor), hepatic and renal function, properties of CYP2C8 perpetrators (dose, treatment course, systemic concentrations, time after discontinuation, inhibitory potency, inhibitory abilities of metabolites on CYP2C8), properties of object drugs (whether the active metabolite of object drug is a CYP2C8 substrate, therapeutic index, stereoselectivity), differences in DDI risk for drugs from similar therapeutic classes, and whether multiple interaction mechanisms are involved. Some botanical supplements showed potential to influence CYP2C8 in vitro or in animal experiments. Conclusion: CYP2C8 is an important but underrecognized DME. This article reviewed its main substrates, perpetrators, DDIs, and methods for predicting interactions, and provided the first comprehensive summary of the factors influencing the interaction magnitude. Such knowledge will enhance the awareness of clinical professionals regarding safe medication for older adults. Further advances will emerge if the gaps in current knowledge and priorities for future research are recognized.

Indexed as

Cytochrome P-450 CYP2C8Cytochrome P-450 CYP2C8 InhibitorsDrug InteractionsHumansPolymorphism, GeneticCYP2C8 protein, humanCytochrome P-450 CYP2C8Cytochrome P-450 CYP2C8 Inhibitorscytochrome P450 2C8drug interactionsolder adultspharmacokineticssafety

Identifiers

PMID40980418
PMCPMC12450030

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.