Journal
EXPERT OPINION ON DRUG SAFETY
Volume 7, Issue 6, Pages 647-662Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14740330802501211
Keywords
drug-induced liver injury; hepatotoxicity; integrative; in vitro; in silico; predictive; systems biology; systems modelling
Categories
Funding
- World Bank
Ask authors/readers for more resources
Background: Liver injury is the most common cause of postmarketing withdrawal of drugs. Traditional animal toxicity testing methods have proved to be imperfect tools for predicting toxicity observed in the clinic. Objective: Predictive methods that integrate data and insights from several in vitro methods to provide a deeper understanding of the impact of a drug on the liver are the need of the hour. Method: A systems approach based on mathematical modelling using the kinetics of biochemical pathways involved in liver homeostasis coupled with in vitro measurements to quantify drug-induced perturbations is described here. Conclusions: Integrating in silico and in vitro methods provides a powerful platform that allows reasonably accurate and mechanistic-level prediction of drug-induced liver injury. The method demonstrates that several physiological situations can be accurately modelled as can the effect of perturbations induced by drugs. it can also be used along with high-throughput 'omic' data to generate testable hypotheses leading to informed decision-making.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available