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Interplay of gender, age and drug properties on reporting frequency of drug-induced liver injury.

Publication ,  Journal Article
George, N; Chen, M; Yuen, N; Hunt, CM; Suzuki, A
Published in: Regul Toxicol Pharmacol
April 2018

We examined the effect of gender, age, and drug properties on liver events reporting frequency (RF) to assess patient- and drug-related risks for drug-induced liver injury (DILI). We performed a data-mining analysis of the WHO VigiBase™ to 1) identify drugs with gender- and age-biased RF and 2) characterize drug properties using the Liver Toxicity Knowledge Base. Age-, gender-specific Empirical Bayes Geometric Mean of relative reporting ratio of liver events with 90% confidence interval (CI) was calculated for 375 drugs with DILI potential. Forty-one drugs showed an increased RF in women, which had a higher prevalence of reactive metabolite formation and mitochondrial dysfunction and transporter inhibition. Fifty-nine drugs showed an increased RF in younger women (<50 yrs), many of which had a signature pattern of hepatocellular injury. In contrast, half of 17 drugs that showed an increased RF in men had a cholestatic pattern. In the older group (≥50 yrs), 17 drugs showed an increased RF and had higher transporter inhibition, Cmax, and plasma protein binding, yet shorter plasma elimination. Specific drug properties were associated with gender- and age-biased liver events RF, suggesting possible interactions of drug properties, gender, and age in DILI development.

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Published In

Regul Toxicol Pharmacol

DOI

EISSN

1096-0295

Publication Date

April 2018

Volume

94

Start / End Page

101 / 107

Location

Netherlands

Related Subject Headings

  • Toxicology
  • Sex Factors
  • Pharmaceutical Preparations
  • Middle Aged
  • Male
  • Humans
  • Female
  • Databases, Factual
  • Chemical and Drug Induced Liver Injury
  • Age Factors
 

Citation

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ICMJE
MLA
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George, N., Chen, M., Yuen, N., Hunt, C. M., & Suzuki, A. (2018). Interplay of gender, age and drug properties on reporting frequency of drug-induced liver injury. Regul Toxicol Pharmacol, 94, 101–107. https://doi.org/10.1016/j.yrtph.2018.01.018
George, Nayana, Minjun Chen, Nancy Yuen, Christine M. Hunt, and Ayako Suzuki. “Interplay of gender, age and drug properties on reporting frequency of drug-induced liver injury.Regul Toxicol Pharmacol 94 (April 2018): 101–7. https://doi.org/10.1016/j.yrtph.2018.01.018.
George N, Chen M, Yuen N, Hunt CM, Suzuki A. Interplay of gender, age and drug properties on reporting frequency of drug-induced liver injury. Regul Toxicol Pharmacol. 2018 Apr;94:101–7.
George, Nayana, et al. “Interplay of gender, age and drug properties on reporting frequency of drug-induced liver injury.Regul Toxicol Pharmacol, vol. 94, Apr. 2018, pp. 101–07. Pubmed, doi:10.1016/j.yrtph.2018.01.018.
George N, Chen M, Yuen N, Hunt CM, Suzuki A. Interplay of gender, age and drug properties on reporting frequency of drug-induced liver injury. Regul Toxicol Pharmacol. 2018 Apr;94:101–107.
Journal cover image

Published In

Regul Toxicol Pharmacol

DOI

EISSN

1096-0295

Publication Date

April 2018

Volume

94

Start / End Page

101 / 107

Location

Netherlands

Related Subject Headings

  • Toxicology
  • Sex Factors
  • Pharmaceutical Preparations
  • Middle Aged
  • Male
  • Humans
  • Female
  • Databases, Factual
  • Chemical and Drug Induced Liver Injury
  • Age Factors