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Novel drug-antidote strategy provides greater control of drug action

DURHAM, N.C. In a discovery that could give physicians more control over the actions of medications, researchers at Duke University Medical Center have developed a novel drug pair a potent anti-coagulant with a matched "antidote."

Using this combination pharmaceutical on-off switch, whose unique properties were demonstrated in animal models, researchers could quickly and effectively neutralize the effects of the drug. The finding could open up a new approach to the development of medications. Instead of developing agents to treat the side effects of existing drugs, researchers could develop matched drug-antidote pairs at the beginning of the drug development process to enable the control of drug activity in patients.

The results of the Duke experiments were published Oct. 17, 2004, as an Advance Online Publication of the journal Nature Biotechnology. The study was supported by the National Institutes of Health (NIH), the American Heart Association, and Duke's Department of Surgery.

"These findings have the possibility to significantly change how we care for heart patients," said Bruce Sullenger, Ph.D., vice chairman of research for Duke's surgery department and senior member of the research team.

Sullenger, and his colleague Chris Rusconi, Ph.D., were inspired by Duke cardiologists who said they needed a reliable blood-thinning agent that they could give to patients without the accompanying risks of bleeding. When bleeding events occur, cardiologists have little recourse except to wait for the drug to be cleared from the body naturally, a potentially time-consuming process. Patients who have received anticoagulants and who then must undergo emergency surgery can also face life-threatening delays, said Sullenger.

"One of the biggest problems we face as cardiologists is that one of the major side effects of drugs we use to 'thin the blood' is bleeding," said cardiologist Robert Califf, M.D., director of the Duk
'"/>

Contact: Richard Merritt
Merri006@mc.duke.edu
919-684-4148
Duke University Medical Center
17-Oct-2004


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