PMID- 32510242
OWN - NLM
STAT- MEDLINE
DCOM- 20210312
LR  - 20210312
IS  - 1744-7607 (Electronic)
IS  - 1742-5255 (Linking)
VI  - 16
IP  - 8
DP  - 2020 Aug
TI  - An update on CYP2C9 polymorphisms and phenytoin metabolism: implications for 
      adverse effects.
PG  - 723-734
LID - 10.1080/17425255.2020.1780209 [doi]
AB  - Introduction Phenytoin is a frequently used drug treatment for epilepsy. Genetic 
      polymorphisms in the metabolism of phenytoin, particularly CYP2C9, are strongly 
      associated with increased plasma concentrations and can result in toxicity. Human 
      leukocyte antigen (HLA) alleles are well-known genetic predictors of certain 
      antiepileptic drug-associated severe cutaneous adverse reactions (SCAR), 
      including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). 
      Recent pharmacogenomic studies show genetic polymorphisms in CYP2C9, as well as 
      HLA alleles, are significantly associated with phenytoin-related SCAR. Areas 
      covered Updated pharmacogenomic information of CYP2C9 variants and HLA alleles 
      involved in phenytoin-associated cutaneous adverse drug reactions (cADRs) are 
      discussed in this article. Expert opinion CYP2C9*3 has been identified as the 
      most significant genetic variant associated with increased phenytoin 
      concentrations and adverse events. Recent pharmacogenomic findings reveal that 
      CYP2C9*3 and HLA alleles, i.e. HLA-B*15:02, HLA-B*13:01, and HLA-B*51:01, are 
      important genetic variants in the occurrence of phenytoin-induced cADRs or SCAR. 
      A phenotype- and population-specific multigene panel can be used before 
      prescribing to predict phenytoin-induced cADRs and further guide optimal dose 
      selection.
FAU - Chang, Wan-Chun
AU  - Chang WC
AUID- ORCID: 0000-0001-7069-7083
AD  - Division of Translational Therapeutics, Department of Pediatrics, Faculty of 
      Medicine, University of British Columbia , Vancouver, British Columbia, Canada.
AD  - British Columbia Children's Hospital Research Institute , Vancouver, British 
      Columbia, Canada.
FAU - Hung, Shuen-Iu
AU  - Hung SI
AUID- ORCID: 0000-0001-6531-5538
AD  - Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, 
      Chang Gung Memorial Hospital , Linkou, Taipei, Taiwan.
AD  - College of Medicine, Chang Gung University , Taoyuan, Taiwan.
AD  - Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology 
      Consortium, Chang Gung Memorial Hospital , Linkou, Taiwan.
AD  - Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial 
      Hospital , Keelung, Taiwan.
FAU - Carleton, Bruce C
AU  - Carleton BC
AUID- ORCID: 0000-0002-4485-4054
AD  - Division of Translational Therapeutics, Department of Pediatrics, Faculty of 
      Medicine, University of British Columbia , Vancouver, British Columbia, Canada.
AD  - British Columbia Children's Hospital Research Institute , Vancouver, British 
      Columbia, Canada.
AD  - Pharmaceutical Outcomes Programme, BC Children's Hospital , Vancouver, British 
      Columbia, Canada.
FAU - Chung, Wen-Hung
AU  - Chung WH
AUID- ORCID: 0000-0003-1681-0959
AD  - Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, 
      Chang Gung Memorial Hospital , Linkou, Taipei, Taiwan.
AD  - College of Medicine, Chang Gung University , Taoyuan, Taiwan.
AD  - Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology 
      Consortium, Chang Gung Memorial Hospital , Linkou, Taiwan.
AD  - Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial 
      Hospital , Keelung, Taiwan.
AD  - Department of Dermatology, Xiamen Chang Gung Hospital, Teaching Hospital of 
      School of Medicine, Tsinghua University , China.
AD  - School of Medicine, Shanghai Jiao Tong University , Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200716
PL  - England
TA  - Expert Opin Drug Metab Toxicol
JT  - Expert opinion on drug metabolism & toxicology
JID - 101228422
RN  - 0 (Anticonvulsants)
RN  - 0 (HLA-B Antigens)
RN  - 6158TKW0C5 (Phenytoin)
RN  - EC 1.14.13.- (CYP2C9 protein, human)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2C9)
SB  - IM
MH  - Anticonvulsants/*administration & dosage/adverse effects/pharmacokinetics
MH  - Cytochrome P-450 CYP2C9/genetics
MH  - Epilepsy/*drug therapy
MH  - HLA-B Antigens/genetics
MH  - Humans
MH  - Pharmacogenetics
MH  - Phenytoin/*administration & dosage/adverse effects/pharmacokinetics
MH  - Polymorphism, Genetic
OTO - NOTNLM
OT  - Adverse drug reaction (ADR)
OT  - CYP2C9
OT  - Stevens-Johnson syndrome (SJS)
OT  - human leukocyte antigen (HLA)
OT  - pharmacogenomics
OT  - phenytoin
OT  - toxic epidermal necrolysis (TEN)
EDAT- 2020/06/09 06:00
MHDA- 2021/03/13 06:00
CRDT- 2020/06/09 06:00
PHST- 2020/06/09 06:00 [pubmed]
PHST- 2021/03/13 06:00 [medline]
PHST- 2020/06/09 06:00 [entrez]
AID - 10.1080/17425255.2020.1780209 [doi]
PST - ppublish
SO  - Expert Opin Drug Metab Toxicol. 2020 Aug;16(8):723-734. doi: 
      10.1080/17425255.2020.1780209. Epub 2020 Jul 16.