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The association between CYP2C9/2C19 polymorphisms and phenytoin maintenance doses in Asian epileptic patients: A systematic review and meta-analysis
Abstract
OBJECTIVE: Therapeutic response to phenytoin (PHT), a first-line antiepileptic drug (AED), is highly variable, in part likely due to genetic factors. Genetic polymorphisms in cytochrome P450 (CYP) 2C9 and CYP2C19 are expected to affect the metabolism of PHT and consequently affect its maintenance doses. We aimed to clarify the effects of genetic polymorphisms in both enzymes on daily PHT maintenance dosage in Asian epileptic patients by meta-analysis. MATERIALS AND METHODS: A systematic literature search was conducted in PubMed and EMBASE for relevant studies published prior to April 14, 2017. RevMan 5.2.3 software was used to analyze the relationship between CYP2C9/2C19 polymorphisms and PHT maintenance doses. RESULTS: A total of 6 studies with 993 patients fulfilling the inclusion criteria were included in our meta-analysis. The homozygous and heterozygous CYP2C19 mutation group (i.e., CYP2C19*2/*2, CYP2C19*3/*3, or CYP2C19*2/*3 group) required significant decrease of PHT maintenance dose. The starting maintenance dose suggested in this group is 4.38 mg/kg/day. Patients with heterozygous CYP2C9 or both heterozygous CYP2C9 and CYP2C19 showed a trend but not a statistically-significant decrease of PHT dose, but dosage adjustment was recommended. CONCLUSION: The meta-analysis indicates that CYP2C9 and CYP2C19 polymorphisms are associated with lower PHT maintenance dosage in Asian epileptic patients. Ethnic differences can influence PHT maintenance dose. .
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Due to genetic differences in pharmacokinetics and pharmacodynamics, clopidogrel, phenytoin, warfarin, clozapine, and carbamazepine had variable efficacy and side-effect profiles in Western and non-Western individuals.
“Due to genetic differences in pharmacokinetics and pharmacodynamics, clopidogrel [29], phenytoin [30], warfarin [31], clozapine [32], and carbamazepine [33] also had variable efficacy and side-effect profiles in Western and non-Western individuals.”
From Hasty generalizations and generics in medical research: A systematic review (2024) · cites this paper as [30]
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Hasty generalizations and generics in medical research: A systematic review
Peters, U., Sherling, H. R., & Chin-Yee, B. (2024) · PLOS ONE · doi:10.1371/journal.pone.0306749 · Cited by 11
Metadata
- Authors
- Liao, K., Liu, Y., Ai, C.-Z., Yu, X., & Li, W.
- Venue
- Int. Journal of Clinical Pharmacology and Therapeutics
- Publisher
- Dustri-Verlgag Dr. Karl Feistle
- Published
- 2018-07-01
- Volume
- 56
- Issue
- 07
- Pages
- 337-346
- ISSN
- 0946-1965 (ISSN-L)
- OpenAlex
- W2809537878
- Cited by
- 41
- References
- 0
- Citations by year
- 2024: 5 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 28 · 2019: 2
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Clinical Pharmacology and Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Health Sciences › Medicine › Pharmacology (medical) › Drug-Induced Adverse Reactions
- Keywords
- phenytoin, CYP2C9 polymorphism, CYP2C19 polymorphism, maintenance dose, pharmacogenetics, epilepsy, antiepileptic drugs, drug metabolism, Asian patients, ethnic differences, dose adjustment
- MeSH terms
- Pharmacogenomic Variants, Anticonvulsants, Epilepsy, Heterozygote, Homozygote, Humans, Pharmacogenetics, Phenytoin, Risk Factors, Chi-Square Distribution, Treatment Outcome, Drug Monitoring, Polymorphism, Single Nucleotide, Asian People, Cytochrome P-450 CYP2C9, Cytochrome P-450 CYP2C19
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