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Dear All,
We are designing a study to demonstrate the bioequivalence between IV
dosing and Sub-Q dosing. Considering the bioavailability difference,
we are planning to administer higher amount of dose for sub-Q (for
example, 120% higher than the IV dose). We have some pre-clinical
information to show that 120% dose given through Sub-Q is comparable
to the dose given through IV. But we are not sure if 120% dose of Sub-
Q will eventually show the equivalence to 100% dose of IV in human
trial.
However, if the bioequivalence can not be demonstrated, it could be
that the 120% Sub-Q dose is too low or too high. In this case, can we
apply any post-hoc adjustment to calculate the adjusted AUC?
I heard that the post-hoc adjustment had been used in some cases when
comparing the equivalence between two different routes. But I could
not find any article or FDA documents on this issue.
Does anyone have experience on this issue? Will the post-hoc
adjustment be acceptable to regulatory agencies?
Thanks for help,
CQ Deng, PhD
Research Triangle Park, NC, USA
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Dear CQ,
Instead of trying to guess the correct s.c. dose that will be
bioequivalent to a certain i.v. dose why not administer the same i.v.
and s.c. dose determine the absolute bioavailability of the s.c.
route of administration?
This is the usual approach.
I hope I understood correctly your dilemma.
radu
[This sounds like a good idea, especially if you expect only a 20%
difference. However, when the expected F is much lower it makes more
sense to increase the dose of the low F product to try and match the
concentrations - db]
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The following message was posted to: PharmPK
Dear CQ,
You might want to look up the regulatory definition of Bioequivalence
in 21 CFR 320.1. It requires that for two dosage forms to be
bioequivalent they must be administered as the same molar amount and
under similar conditions. I understand what you are trying to do with
the study but I do not think bioequivalence applies here, especially
since you will have some difficulty getting the same rate of
availability from an IV and SQ dose.
Art Straughn, Pharm.D.
Professor Emeritus and Director
UT Drug Research Laboratory
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