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EnglishThe idiosyncratic nature of drug-induced liver injury (Dili) represents a current challenge for drug developers, regulators and clinicians. The myriad of agents (including medications, herbals, and dietary supplements) with recognized Dili potential not only strengthens the importance of the post-marketing phase, when urgent withdrawal sometimes occurs for rare unanticipated liver toxicity, but also shows the imperfect predictivity of pre-clinical models and the lack of validated biomarkers beyond traditional, non-specific liver function tests. After briefly reviewing proposed key mechanisms of Dili, we will focus on drug-related risk factors (physiochemical and pharmacokinetic properties) recently proposed as predictors of Dili and use cyclin-dependent kinase 4/6 inhibitors, relatively novel oral anticancer medications approved for breast cancer, as a case study to discuss the feasibility of early detection of Dili signals during drug development: published data from pivotal clinical trials, unpublished post-marketing reports of liver adverse events, and pharmacokinetic properties will be used to provide a comparative evaluation of their liver safety and gain insight into drug-related risk factors likely to explain the observed differences.
| Titolo: | Strategies for early prediction and timely recognition of drug-induced liver injury: The case of cyclin-dependent kinase 4/6 inhibitors | |
| Autore/i: | Raschi E.; De Ponti F. | |
| Autore/i Unibo: | ||
| Anno: | 2019 | |
| Rivista: | ||
| Digital Object Identifier (DOI): | http://dx.doi.org/10.3389/fphar.2019.01235 | |
| Abstract: | The idiosyncratic nature of drug-induced liver injury (Dili) represents a current challenge for drug developers, regulators and clinicians. The myriad of agents (including medications, herbals, and dietary supplements) with recognized Dili potential not only strengthens the importance of the post-marketing phase, when urgent withdrawal sometimes occurs for rare unanticipated liver toxicity, but also shows the imperfect predictivity of pre-clinical models and the lack of validated biomarkers beyond traditional, non-specific liver function tests. After briefly reviewing proposed key mechanisms of Dili, we will focus on drug-related risk factors (physiochemical and pharmacokinetic properties) recently proposed as predictors of Dili and use cyclin-dependent kinase 4/6 inhibitors, relatively novel oral anticancer medications approved for breast cancer, as a case study to discuss the feasibility of early detection of Dili signals during drug development: published data from pivotal clinical trials, unpublished post-marketing reports of liver adverse events, and pharmacokinetic properties will be used to provide a comparative evaluation of their liver safety and gain insight into drug-related risk factors likely to explain the observed differences. | |
| Data stato definitivo: | 2020-02-04T23:48:07Z | |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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