When life-threatening side effects are linked to pharmaceuticals already on the market, it can lead to black box warnings or even market withdrawal. When this potential for injury is found during clinical trials before the medication has been approved, it can stop development in its tracks resulting in a waste of time and resources.
“We’re trying to be smarter in our approach to drug development,” says Kim Brouwer, a researcher with the University of North Carolina. Brouwer and colleagues have partnered with the Drug Induced Liver Injury (DILI)-sim Initiative, a group of life science companies led by the Hamner Institutes for Health Sciences, to study the causes of DILI.
Drug induced liver injuries are the most common cause of acute liver failure and one of the primary reasons for failure of pharmaceutical agents during drug development.
The study grew out of an interest into the type 2 diabetes drug troglitazone, which in 2000 was pulled from the market after 63 people died as a result of acute liver failure. However, the underlying cause of the deaths remained unknown.
“Unfortunately, the hepatotoxic potential of drug candidates is currently not well understood from in vitro screening or standard preclinical testing, said lead author Kyunghee Yang.
By generating experimental data generated from human liver cells with the DILI-sim computational model, researchers were able to predict human drug induced liver injury for the first time.
“The hope is that we will be able to effectively identify early on which drugs or compounds have liver liability for damage or even death and protect the public from these negative events,” Brouwer says.
Several type 2 diabetes drugs have been linked to serious side effects, including cancer. In 2011, the Food and Drug Administration (FDA) warned that Actos had been linked to several cases of bladder cancer. The drug was not pulled from the market but bladder cancer warnings were placed on the drug’s label. More recently, the drugs Januvia and Byetta have been linked to acute pancreatitis and pancreatic cancer, and have come under investigation by the FDA.
Source: Daily Tar Heel