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...an hepatotoxicity were not identified as having this potential in nonclinical animal testing [2]. Many drugs have been withdrawn from the market or have received restrictions and warnings due to DILI =-=[3]-=-. DILI information and guidance for pharmaceutical industries has been released by regulatory agencies such as the U.S. Food and Drug Administration (FDA) (http://www.fda.gov/downloads/ Drugs/Guidance...

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...hus protecting humans from this damage, a consortium determined that about half of the drugs that cause human hepatotoxicity were not identified as having this potential in nonclinical animal testing =-=[2]-=-. Many drugs have been withdrawn from the market or have received restrictions and warnings due to DILI [3]. DILI information and guidance for pharmaceutical industries has been released by regulatory...

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...nce the predictability of DILI, novel approaches have been explored by many researchers. Notable examples include (a) development of new DILI biomarkers [6], (b) introduction of highcontent screening =-=[7]-=-, (c) adoption of more sensitive animal models [8,9,10], and (d) utilization of toxicogenomics [11]. Most of these investigations are focused on developing biomarkers using either animal or in vitro m...

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...als as well as regulatory agencies. It is the leading cause of acute liver failure, which has a high mortality rate (30%) as treatment is limited due to the availability of livers for transplantation =-=[1]-=-. Although many dangerous drugs are identified during animal testing thus protecting humans from this damage, a consortium determined that about half of the drugs that cause human hepatotoxicity were ...

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...statistical power of the trials – the risk of severe DILI of an idiosyncratic nature is very low per exposed subject, while clinical trials are usually carried out with only several thousand patients =-=[5]-=-, rendering them significantly underpowered to predict rare DILI events. To enhance the predictability of DILI, novel approaches have been explored by many researchers. Notable examples include (a) de...

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...orious example, five subjects in a phase 2 clinical trial experienced fatal hepatotoxicity induced by fialuridine, an investigational nucleoside analogue that showed no liver damage in animal studies =-=[4]-=-. Out of 221 pharmaceuticals, the overall concordance of liver toxicity in humans and experimental animals is as low as 55%, which is in sharp contrast with the concordance of other target organs such...

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...derpowered to predict rare DILI events. To enhance the predictability of DILI, novel approaches have been explored by many researchers. Notable examples include (a) development of new DILI biomarkers =-=[6]-=-, (b) introduction of highcontent screening [7], (c) adoption of more sensitive animal models [8,9,10], and (d) utilization of toxicogenomics [11]. Most of these investigations are focused on developi...

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...ave been explored by many researchers. Notable examples include (a) development of new DILI biomarkers [6], (b) introduction of highcontent screening [7], (c) adoption of more sensitive animal models =-=[8,9,10]-=-, and (d) utilization of toxicogenomics [11]. Most of these investigations are focused on developing biomarkers using either animal or in vitro models for predicting DILI in humans. This still would i...

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...ave been explored by many researchers. Notable examples include (a) development of new DILI biomarkers [6], (b) introduction of highcontent screening [7], (c) adoption of more sensitive animal models =-=[8,9,10]-=-, and (d) utilization of toxicogenomics [11]. Most of these investigations are focused on developing biomarkers using either animal or in vitro models for predicting DILI in humans. This still would i...

Citation Context

...ave been explored by many researchers. Notable examples include (a) development of new DILI biomarkers [6], (b) introduction of highcontent screening [7], (c) adoption of more sensitive animal models =-=[8,9,10]-=-, and (d) utilization of toxicogenomics [11]. Most of these investigations are focused on developing biomarkers using either animal or in vitro models for predicting DILI in humans. This still would i...

Citation Context

...xamples include (a) development of new DILI biomarkers [6], (b) introduction of highcontent screening [7], (c) adoption of more sensitive animal models [8,9,10], and (d) utilization of toxicogenomics =-=[11]-=-. Most of these investigations are focused on developing biomarkers using either animal or in vitro models for predicting DILI in humans. This still would involve synthesis of the drug and elaborate t...