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Dear All,
I am dealing with a situation where an oral hypoglycemic agent has to be
administered with a glucose solution (for safety reason). What could be
the
anticipated effect of this administration (and more likely to have an
impact
on the PK profile of the drug):
-modification of the dissolution of the dosage form?
-modification of the gastric motility?
-modification of the gastric/intestinal blood flow?
-anything else?
My second question is: could this glucose solution (20% glucose, 240mL)
be
considered as "food", and as a consequence the study would be not
qualified
as "fasting"?
Any input or experience on the subject would be greatly appreciated.
Thanks a lot,
Corinne
Corinne Campanella
BIOVAIL, Canada
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Dear Corinne
-anything else?
Instead of Glucose you should consider sucrose solution (simply put
diluted unflavoured syrup). You may have to go for glucose tolerance
test if you decide to administer glucose solution.
Keep handy glucometer and enogh stripes, and emergency measures for
sudden hypoglycemia.
-modification of the dissolution of the dosage form? ....
Add glucose or sucrose to your dissolution media and check for
differences
-modification of the gastric motility? ....
does not seem to be a clinically significant possibility unless you
give extreme tonicity fluid in large quantity.
-modification of the gastric/intestinal blood flow? ...
most unlikely. Do you have reasons to think aout such a possibility?
Thanks and Regards
Dr.Prashant
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The following message was posted to: PharmPK
Hello Corinne,
I've just a couple of thoughts about your situation.
I am not sure that your vehicle will have any effect on dissolution. If
it
has it should be a positive one.
I would certainly consider this study as performed in a fasting state
because you will only dose liquids. In this case I anticipate no
influence
on gastric motility and no significant intestinal event to consider
that you
are in a fed state.
Best regards,
Frederic Doc
Pfizer Global R&D
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The glucose solution should not be consider as food. It should not
increase the dissolution of the drug significantly as compared to the
pure water.
The study should be considered as fasting.
Furthermore, in order to prevent hypoglycemia, additional glucose
should be administered to the subjects within the first 4 hours
post-dose; 50-60 ml every half an hour. This will increase the volume
of liquid that is usually administered to subjects in fasting study and
this can really improve drug dissolution. However, the procedure should
be acceptable since is required to ensure the safety of the subjects.
Hope this helps,
radu
Radu D. Pop
Director Biopharmaceutics
Pharma Medica Research Inc.
966 Pantera Drive
Mississauga, Ontario
Canada, L4W 2S1
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The following message was posted to: PharmPK
Dear colleagues:
I have measured gastric emptying of water and various glucose solutions
dozens of times in humans. 500ml of 10% glucose (which incidentally
tastes
very weak) empties at about half the rate of water. Typical half
emptying
time means for water are about 5-7 minutes and they would be around 12
minutes for glucose 10%. Accordingly, I agree with Prashant, it's
going to
be a very small effect on absorption rates unless you invoke osmotically
induced gastric stasis with supra-normal concentrations.
Andrew Sutton
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