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DewDiligence

04/06/11 1:12 PM

#117738 RE: dewophile #117710

i agree [first-step phosphorylation in vivo] makes all the difference when it comes to potency - which can relate to resistance since you can shorten duration of viral exposure to drug - but i don't think it impacts on the inherent resistance barrier of the final active moiety.

I would argue that sub-therapeutic dosing of the active triphosphate metabolite (another way of saying that potency is inadequate) is a larger cause of drug resistance than any deficiencies in the inherent barriers of the motieties for the HCV nukes that have actually been tested.