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Cited by 127Pharmacogenetics and Drug MetabolismDrug Transport and Resistance MechanismsDrug-Induced Hepatotoxicity and Protection

CYP3A4 and CYP3A5: the crucial roles in clinical drug metabolism and the significant implications of genetic polymorphisms

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Zhang, Yuqing, Wang, Ziying, Wang, Yuchao, Jin, Weikai, Zhang, Zheyan, Jin, Lehao, Qian, Jianchang, Zheng, Long·2024·PeerJ
DOI 10.7717/peerj.18636PMC PMC11625447
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Abstract

CYP3A, a key member of the cytochrome P450 (CYP450) superfamily, is integral to drug metabolism, processing a substantial portion of medications. Their role in drug metabolism is particularly prominent, as CYP3A4 and CYP3A5 metabolize approximately 30–50% of known drugs. The genetic polymorphism of CYP3A4/5 is significant inter-individual variability in enzymatic activity, which can result in different pharmacokinetic profiles in response to the same drug among individuals. These polymorphisms can lead to either increased drug toxicity or reduced therapeutic effects, requiring dosage adjustments based on genetic profiles. Consequently, the study of the enzymatic activity of CYP3A4/5 gene variants is of great importance for the formulation of personalized treatment regimens. This article first reviews the role of CYP3A4/5 in drug metabolism in the human body, including inhibitors and inducers of CYP3A4/5 and drug-drug interactions. In terms of genetic polymorphism, it discusses the detection methods, enzymatic kinetic characteristics, and clinical guidelines for CYP3A5. Finally, the article summarizes the importance of CYP3A4/5 in clinical applications, including personalized therapy, management of drug-drug interactions, and adjustment of drug doses. This review contributes to the understanding of the functions and genetic characteristics of CYP3A4/5, allowing for more effective clinical outcomes through optimized drug therapy.

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  • These enzymes are responsible for metabolizing 70% of clinically prescribed drugs.

    “These enzymes are responsible for metabolizing 70% of clinically prescribed drugs22,23, establishing this timepoint as pivotal for investigating drug metabolism, interactions, and toxicity.”

    From ​Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology (2026) · cites this paper as [23]

    The Introduction says CYP3A4/5 are involved in metabolizing 30–50% of clinical drugs, not 70%. It gives a higher estimate, 75–90%, for the broader CYP450 enzyme family, which does not support assigning 70% to CYP3A4/5. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Zhang, Y., Wang, Z., Wang, Y., Jin, W., Zhang, Z., Jin, L., Qian, J., & Zheng, L.
Affiliations
  • Wenzhou Medical University (CN)
  • Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
Corresponding author
  • Qian, Jianchang
  • Zheng, Long
ORCID
Venue
PeerJ
Publisher
PeerJ
Published
2024-12-05
Volume
12
Pages
e18636
ISSN
2167-8359 (ISSN-L)
DOI
10.7717/peerj.18636
PMC
PMC11625447
OpenAlex
W4405083111
Cited by
127
References
4
Citations by year
2026: 74 · 2025: 52 · 2022: 1
FWCI
9.95
Type
journal article
Language
en
Open access
Licence
Locations
  • PeerJ (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Wenzhou Medical University
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
CYP3A4, CYP3A5, cytochrome P450, drug metabolism, genetic polymorphism, interindividual variability, pharmacokinetics, drug-drug interactions, CYP3A4 inhibitors, CYP3A4 inducers, personalized medicine, dose adjustment, pharmacogenetics
MeSH terms
Drug Interactions, Pharmaceutical Preparations, Humans, Polymorphism, Genetic, Cytochrome P-450 CYP3A, Precision Medicine

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