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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • George, N; Chen, M; Yuen, N; Hunt, CM; Suzuki, A

Published Date

  • April 2018

Published In

Volume / Issue

  • 94 /

Start / End Page

  • 101 - 107

PubMed ID

  • 29407200

Pubmed Central ID

  • 29407200

Electronic International Standard Serial Number (EISSN)

  • 1096-0295

Digital Object Identifier (DOI)

  • 10.1016/j.yrtph.2018.01.018

Language

  • eng

Conference Location

  • Netherlands