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UMN researchers create new antidote for acetaminophen poisoning

Acetaminophen has become the go-to fix for minor aches and pains. People often consider the over-the-counter drug to be harmless, but if taken at a high dose, it can be significantly toxic. The margin between benefit and harm is much smaller for acetaminophen than other pain medications.

It’s estimated that more than 50,000 people in the USA alone visit the emergency room each year for liver toxicity due to acetaminophen poisoning. In addition, as people age, their liver loses the ability to efficiently detoxify acetaminophen. Over time, what seems like a small, regular dose, may actually put extra strain on the body.

“It’s concerning,” said researcher Swati More, Ph.D., assistant professor in the Center for Drug Design. “People rarely worry about acetaminophen overdose, but even just one pill more than the recommended daily dose could be toxic over time.”

In fact, a 2008 FDA report found that a large number of people using acetaminophen take a toxic dose regularly. For years, unit doses of acetaminophen were limited to 500 mg, but in 2011 the FDA tightened those restrictions to just 325 mg.

More and Robert Vince, Ph.D., Professor and Director of the Center for Drug Design, discovered a potential new drug that works as an antidote to acetaminophen poisoning. It’s named ψ-Glutathione (Pseudo-Glutathione), similar to the naturally-occurring compound glutathione. A report of the compound’s efficacy was recently published in Chemical Research in Toxicology.

“Our antidote appears to be extraordinarily safe. In mice, we found that it caused no toxicity alone or in combination with acetaminophen,” More said.

In animal models, ψ-Glutathione appears to be superior to N-acetylcysteine, which is the only antidote currently available in an emergency clinical setting.

The current antidote to acetaminophen poisoning is available orally or through an IV, but it’s associated with gastrointestinal side effects and allergic reaction. If not taken quickly after the overdose has occurred, it loses effectiveness. In fact, 8 hours after the overdose it only offers moderate protection, if that.

“The treatment we created is effective even after delayed administration, and it can be taken orally,” Vince said.

A patent application has been filed on the compound and Vince and More hope to translate their findings into a clinical trial. Vince and More are working closely with the Office for Technology Commercialization to help bridge the gap between lab and the marketplace.

“There has been significant commercial interest in this compound and Drs. Vince and More’s research, said Rebecca Gerber, associate director in the Office for Technology Commercialization. “This is yet another example of exciting and commercially relevant research being completed at the University, and specifically within the Center for Drug Design.”

The thought is this new compound could be combined with acetaminophen to reduce the risk of toxicity in those medications, and potentially reduce the number of accidental acetaminophen overdoses.

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