Pharmacy school researchers studying deadly diabetes drug

In 1997, 63 individuals died from acute liver failure after taking a diabetes drug called troglitazone. 

The drug was eventually withdrawn from the market in 2000, but the underlying cause of these deaths remained unknown. However, researchers at UNC Eshelman School of Pharmacy have recently solved this medical mystery. 

In 2011, UNC formed a partnership with the DILI-sim Initiative, a group of life science companies led by the Hamner Institutes for Health Sciences.  

“The DILIsym with a 'y' is the trademark for the software produced by the DILI-sim Initiative,” said Paul Watkins, one of the developers of the computer software and a UNC professor. The research team at UNC used this computer software in their study of drug induced liver injury (DILI). 

“Drug-induced liver injury is the most common cause of acute liver failure, and is one of the primary reasons for the failure of pharmaceutical agents during drug development,” said Kyunghee Yang, lead author of the study. 

“Unfortunately, the hepatotoxic potential of drug candidates is currently not well predicted from in vitro screening or standard preclinical testing," she said. "If DILI cases are reported after the drug is approved, it might lead to blackbox warnings or withdrawal of drugs from worldwide markets, such as troglitazone.”

The goal of the research was therefore to develop a smarter computational model for predicting DILI in patients who are taking the drugs. 

“It’s a waste of time and resources when drugs don’t work,” said Kim Brouwer, whose liver research data was used in the study. “We’re trying to be smarter in our approach to drug development and identify which drugs cause damage to the liver early on.” 

By integrating the experimental data generated from human liver cells in Brouwer’s research with the DILIsym computational model, they were able to predict human drug induced liver injury for the first time. 

“The liver is more vulnerable primarily because this organ processes almost everything we consume. The blood supply goes to the liver before the rest of the body, so the liver is our first defense against toxic substances,” Brouwer said. 

“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.”

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