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We are dosing anti-diabetic compounds for 7 days in diabetic db/db mice
using ALZET mini-osmotic pumps implanted SQ. The drugs are formulated
in 0.5% methylcellulose. We just made the strange observation that
after an overnight fast (on the 7th day), the blood glucose levels in
these animals dropped very little if at all (including the vehicle
controls). Other animals from the same age cohort that were similarly
fasted but not dosed have the expected dramatic reduction in blood
glucose levels. Having ruled out all the trivial explanations (like
someone forgot to fast the animals!), the only thing I can think of is
that we formulated our compounds in methylcellulose, which is
essentially polymerized glucose. Does anyone know whether mice can
break down methylcellulose into glucose to any extent when SQ dosed
continuously?
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As a complement of information to your question: what is the dose
volume of MC administered in mL/kg/hr?
Jean-Pierre Moreau
Biopharmacopae Design International
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Dosing was using 1ul/hr mini-pumps and the animals are 35-40g in weight.
For what it is worth, 0.5% MC does not read in the glucometers we are
using (actually, it gives an "error" reading), but I haven't tried
spiking blood with MC to see if that could be the problem.
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This volume basically correspond to 25 uL/kg/hr wich is very low,
spiking blood will give you an idea but you will miss the tissue
metabolism issue (if posssible) I would rather dose an untreated
fasted mouse with 0.1 mL of MC by the SC route and measure blood
glucose prior to and ca 30 minutes after the administration this will
give you an idea if MC is responsible for this.
Good Luck
Jean-Pierre Moreau
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)