Drugs prescribed for various medical conditions can cause harmful
liver side effects. Lab experiments with liver cells can help reveal the
underlying molecular mechanisms by which these drugs cause liver
damage, which could inform better prevention and treatment efforts.
However, lab experiments alone cannot reliably predict actual effects in
To improve translation of lab data to patients, Christoph Thiel of RWTH Aachen University, Germany, and colleagues recently developed a new strategy that uses computational modeling to simulate how liver cells in the body respond to different doses of different drugs. The approach integrates experimental observations with knowledge of how drugs are distributed and metabolized after they enter the body.
The researchers had previously demonstrated their approach in a proof-of-concept study. In the new study, the approach was applied to simulate and compare the potentially toxic liver effects of fifteen different drugs at clinically relevant doses.
While further validation is required, the method has the potential to lead to faster diagnosis of toxic liver side effects in patients. It could help reveal which gene transcripts could serve as early signs of toxicity and which drug combinations might be particularly dangerous, for both new and existing drugs.
"Consistently applied to the design of clinical development programs, the approach presented has the potential to early identify medical and economic risks of new drugs," says study co-author Lars Kuepfer.