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Dear All,
I am conducting my first pharmacokinetic studies. I am
studying buccal administration of insulin compared to subcutaneous
injection of insulin solution. While doing calculations, I am having
a basic doubt. I came across journal articles where the AUC of
insulin in plasma for the subcutaneous group has been calculated till
infinity, while the AAC of blood glucose of the subcutaneous group
has been calculated till 8 hrs (the time for buccal study also). Can
anybody please explain why two different time periods have been
considered for the two calculations for the same group? Please help.
Thanks.
Nilanjana.
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The following message was posted to: PharmPK
Nilanjana,
You wrote:
> I came across journal articles where the AUC of
> insulin in plasma for the subcutaneous group has been calculated till
> infinity, while the AAC of blood glucose of the subcutaneous group
> has been calculated till 8 hrs (the time for buccal study also). Can
> anybody please explain why two different time periods have been
> considered for the two calculations for the same group?
The choice of integration interval (0 to infinity, or 0 to 8 hours)
can be made based on basic PK theory. For single doses the AUC 0 to
infinity should be the same as the AUC in an 8 h dosing interval at
steady state with doses given every 8 hours. If you want to show that
the drug has first-order accumulation properties then you would
compare AUC 0 to infinity after a single dose with AUC 0 to 8 h at
steady state with an 8 h dosing interval.
But these simple ideas won't work for insulin and glucose.
AUC from 0 to infinity for insulin and for glucose is tricky to do
because these are endogenous substances and you have to figure out
some way to subtract the baseline which varies during the day. It is
probably easier to interpret the results by just comparing the AUC
for insulin over some fixed interval e.g. 0 to 8h or 0 to 24h. There
is no expectation that glucose would have simple first order kinetics
because we know thats its elimination depends on insulin as well as
glucose concs.
In the case of glucose AUC it is being used as a response marker for
the effect of insulin on glucose. You should choose the AUC of
glucose to be anything convenient but presumably it would be nice if
you can observe the glucose return close to its pre-treatment
baseline (assuming you give just one dose of insulin).
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford
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Thanks a lot for your valuable comments. Still I have some confusion.
Then if my data returns to baseline values then I should consider AUC
(till infinity) irrespective of the route of administration. Please
confirm if I am right.
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The following message was posted to: PharmPK
Nilanjana Das wrote:
> Then if my data returns to baseline values then I should consider AUC
> (till infinity) irrespective of the route of administration. Please
> confirm if I am right.
If you have a varying circadian baseline glucose (and insulin) then
there is no simple way to calculate AUC 0 to infinity for glucose.
The simplest thing to do is to calculate AUC 0 to whenever you think
the glucose has returned to baseline e.g. 8 h or 24 h or whatever you
observed.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.aaa.auckland.ac.nz tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford
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Thanks a lot for your valuable inputs. Is it always that the
pharmalogical availability and bioavailability should be equal in
value. In my analysis I am finding difference in their values.
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