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moderate renal impairment (eGFR 30-45 ml/min) has been observed to increase plasma levels of sitagliptin 2-fold, and severe renal impairment can increase plasma levels 4-fold
So, even though the total drug level in our blood is in the nanomolar range, its so tightly bound to protein that the active level in our blood thats free to actually interact with tissue receptors is like a hundred times smaller, at least down in the picomolar range
Numerous mitochondrial proteins contain essential thiol residues
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