PMID- 22357454
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20181201
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 91
IP  - 4
DP  - 2012 Apr
TI  - Lapatinib-induced liver injury characterized by class II HLA and Gilbert's 
      syndrome genotypes.
PG  - 647-52
LID - 10.1038/clpt.2011.277 [doi]
AB  - Lapatinib is a clinically important component of the treatment for HER2-positive 
      metastatic breast cancer and has an acceptable safety profile. 
      Lapatinib-associated Hy's Law cases have been characterized using human leukocyte 
      antigen (HLA) DQA1*02:01/DRB1*07:01 and Gilbert's syndrome UGT1A1*28/*28 
      genotypes. The HLA-positive cases had higher alanine aminotransferase (ALT) 
      elevation, whereas the HLA-negative cases had a higher incidence of Gilbert's 
      syndrome. The findings of our study, which extend this HLA association to 
      lapatinib-associated serious liver injury, emphasize the importance of Gilbert's 
      syndrome in the interpretation of Hy's Law and may lead to methods for enhancing 
      patient safety.
FAU - Spraggs, C F
AU  - Spraggs CF
AD  - Genetics Department, GlaxoSmithKline Research & Development, Stevenage, UK. 
      colin.f.spraggs@gsk.com
FAU - Parham, L R
AU  - Parham LR
FAU - Hunt, C M
AU  - Hunt CM
FAU - Dollery, C T
AU  - Dollery CT
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
DEP - 20120222
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*07:01:01 antigen)
RN  - 0 (Quinazolines)
RN  - 0VUA21238F (Lapatinib)
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/biosynthesis/genetics
MH  - Chemical and Drug Induced Liver Injury/epidemiology/*genetics/immunology
MH  - Genotype
MH  - Gilbert Disease/drug therapy/*genetics/immunology
MH  - Glucuronosyltransferase/biosynthesis/*genetics
MH  - HLA-DQ alpha-Chains/biosynthesis/*genetics
MH  - HLA-DRB1 Chains/biosynthesis/*genetics
MH  - Humans
MH  - Incidence
MH  - Lapatinib
MH  - Quinazolines/*adverse effects
EDAT- 2012/02/24 06:00
MHDA- 2012/05/09 06:00
CRDT- 2012/02/24 06:00
PHST- 2012/02/24 06:00 [entrez]
PHST- 2012/02/24 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
AID - clpt2011277 [pii]
AID - 10.1038/clpt.2011.277 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2012 Apr;91(4):647-52. doi: 10.1038/clpt.2011.277. Epub 2012 
      Feb 22.