| アブストラクト | 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 (<50yrs), 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 (>/=50yrs), 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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| ジャーナル名 | Regulatory toxicology and pharmacology : RTP |
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| 投稿日 | 2018/2/7 |
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| 投稿者 | George, Nayana; Chen, Minjun; Yuen, Nancy; Hunt, Christine M; Suzuki, Ayako |
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| 組織名 | Department of Medicine, University of Arkansas for Medical Sciences, Little Rock,;AR, USA.;Division of Bioinformatics and Biostatistics, The FDA's National Center for;Toxicological Research, Jefferson, AR, USA.;Global Patient Safety, UCB BioSciences Inc., Raleigh, NC, USA.;Department of Medicine, Duke University, Durham, NC, USA; Department of Medicine,;Durham VA Medical Center, Durham, NC, USA.;Durham VA Medical Center, Durham, NC, USA. Electronic address:;ayako.suzuki@duke.edu. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/29407200/ |
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