Absorption Systems Scientists Publish Peer-Reviewed Paper on Reactive Drug Metabolites
8/20/2013 10:12:14 AM
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EXTON, Pa., Aug. 20, 2013 /PRNewswire/ -- The preclinical contract research organization Absorption Systems, a global leader in pharmacokinetic testing of drugs and safety testing of medical devices, announces the publication of a peer-reviewed paper in the highly respected journal Chemico-Biological Interactions. The lead author was Igor Mezine, Ph.D. In the paper, company scientists studied the metabolism of troglitazone, a drug that was once indicated for Type 2 diabetes but was withdrawn from the market in 2000 due to numerous cases of liver failure.
Reactive metabolites of troglitazone had been described previously and could be responsible, at least in part, for the liver toxicity observed in many patients who took the drug before its withdrawal. Because of their transient nature and the fact that they are often present at low levels, reactive metabolites are generally identified indirectly, by capture (trapping) with a reducing agent such as glutathione. Then the structure of the metabolite is elucidated by determining the structure of its glutathione conjugate. By combining several advances in trapping and analytical technology, the Absorption Systems team identified several novel reactive metabolites, in addition to ones that had been reported by others.
In addition, the work is unique in that the test system consisted of intact human hepatocytes, probably the most physiologically relevant liver model other than the human body itself. Use of hepatocytes enabled the scientists to hypothesize a surprising explanation for their results, which could explain many clinical observations of unexpected liver toxicity, not just with troglitazone but many other drugs as well. That hypothesis is currently being tested.
Ismael Hidalgo, Chief Scientist of Absorption Systems, commented that "We are pretty excited about this line of research, which seems to be leading us in a surprising direction. If we can document a novel explanation for idiosyncratic drug toxicity, that could be very significant."
About Absorption Systems
Absorption Systems, founded in 1996, assists pharmaceutical, biotechnology and medical device companies in identifying and overcoming ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) barriers in the development of drugs, biologics and medical devices. The company's mission is to continually develop innovative research tools that can be used to accurately predict human outcomes or to explain unanticipated human outcomes when they occur. The CellPort Technologies® platform, a suite of human cell-based test systems for drug transporter characterization, exemplifies Absorption Systems' commitment to innovation and is soon to be an industry standard for in vitro drug interaction assessment. Absorption Systems, with facilities near Philadelphia, PA, in San Diego, CA, and in Panama, serves customers throughout the world. For information on the company's comprehensive contract services and applied research programs, please visit www.absorption.com.
SOURCE Absorption Systems
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