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Abstract: A major concern in drug development is the potential for chemical injury to the liver. Drugs account for 1/3~1/2 of acute liver failures, yet underlying toxicity mechanisms are poorly understood. Adverse reactions are often detected too late, as with troglitazone, an antidiabetic drug introduced in 1997 and withdrawn in 2000 after several cases of liver failure. Predictions are more limi... read moreted with multi-drug interactions, common among patients with chronic ailments like diabetes. Here we develop a microfluidic reactor for the culture of HepG2 cells and the establishment of a steady state drug gradient. Traditional in vitro experiments explore the metabolic effects of troglitazone on HepG2 cells and the interactions between rosiglitazone and metformin (common antidiabetic compounds). LC-MS methods are developed for the detection of drugs and key metabolites. This research expands our knowledge drug metabolism in the liver and introduces a physiologically relevant platform for the testing of drug interactions.
Thesis (M.S.)--Tufts University, 2011.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: Kyongbum Lee.
Committee: Daniel Ryder, and Catherine Kuo.
Keyword: Chemical engineering.read less
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