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I am testing the pancreas toxicity of a compound in rats. The lower dose (20mg/Kg) have a greater weight loss, along with increased food and water intake, which is an indication of diabetes, while the higher dose (100mg/Kg) didn't show such a sign. Oral glucose tolerance test confirmed this with a much higher plasma glucose from the lower dose.
I have suspected a CPY450 enzyme induction by the higher dose, because this compound have a enzyme induction ability. Also, there's a possibility that this compound induced the ABC transporter in pancreas and resulted in a lower pancreas drug concentration. Is there any literature discussing about this issue, or have anyone met such phenomenon before?
Thanks a lot.
-- Yours, Xinting Wang
Key Laboratory of Drug Metabolism & Pharmacokinetics
China Pharmaceutical University
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