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Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes.

Publication ,  Journal Article
Spraggs, CF; Parham, LR; Hunt, CM; Dollery, CT
Published in: Clin Pharmacol Ther
April 2012

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.

Duke Scholars

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

April 2012

Volume

91

Issue

4

Start / End Page

647 / 652

Location

United States

Related Subject Headings

  • Quinazolines
  • Pharmacology & Pharmacy
  • Lapatinib
  • Incidence
  • Humans
  • HLA-DRB1 Chains
  • HLA-DQ alpha-Chains
  • Glucuronosyltransferase
  • Gilbert Disease
  • Genotype
 

Citation

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Spraggs, C. F., Parham, L. R., Hunt, C. M., & Dollery, C. T. (2012). Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes. Clin Pharmacol Ther, 91(4), 647–652. https://doi.org/10.1038/clpt.2011.277
Spraggs, C. F., L. R. Parham, C. M. Hunt, and C. T. Dollery. “Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes.Clin Pharmacol Ther 91, no. 4 (April 2012): 647–52. https://doi.org/10.1038/clpt.2011.277.
Spraggs CF, Parham LR, Hunt CM, Dollery CT. Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes. Clin Pharmacol Ther. 2012 Apr;91(4):647–52.
Spraggs, C. F., et al. “Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes.Clin Pharmacol Ther, vol. 91, no. 4, Apr. 2012, pp. 647–52. Pubmed, doi:10.1038/clpt.2011.277.
Spraggs CF, Parham LR, Hunt CM, Dollery CT. Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes. Clin Pharmacol Ther. 2012 Apr;91(4):647–652.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

April 2012

Volume

91

Issue

4

Start / End Page

647 / 652

Location

United States

Related Subject Headings

  • Quinazolines
  • Pharmacology & Pharmacy
  • Lapatinib
  • Incidence
  • Humans
  • HLA-DRB1 Chains
  • HLA-DQ alpha-Chains
  • Glucuronosyltransferase
  • Gilbert Disease
  • Genotype