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What may be the effect of the different volumes of water administered
on the bioequivalence estimation? Specifically, if in first period,
subject consumed 240 ml, however, in next period, he could take only
230 ml. How significant is this difference?
Thanks and regards
Kshitij
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Dear Mr. Kshitij,
Two period, cross-over study is designed to minimise / eliminate
intersubject variability. We can estimate intersubject variability by
keeping other regulatory variables constant during both the periods.
Some examples of regulatory variable are as follows.
A) Amount of drinking water during dosing / Calories of food consumed
during study [can affect absorption: so Amount of drinking water
during dosing / Calories of food consumed during both period of the
study must be same. Food should be provided at the same time before
(if applicable) and after dosing during both the periods]
B) Consumption of caffein / drugs of abuse / alcohol (can alter
Pharmacokinetics: so caffein / drugs of abuse / alcohol must not be
consumed before 2 days of dosing and during study)
C) Posture compliance after dosing (affect absorption: so same
posture must be maintained by subjects for certain time after dosing
in both the period).
Regards,
Sumanta
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The following message was posted to: PharmPK
Hi Kshitij,
I would expect the impact on the study to be minimal, and not
significant
from a clinical or pharmacokinetic standpoint. You are talking about
less
than a 5% difference in volume. Hope this helps,
-Dave
--
David Dubins, B.A.Sc., Ph.D.
Manager Biopharmaceutics
Allied Research International Inc.
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hi Kshitij,
Though it is minimum amount of water, why dont you considered this as
deviation of protocol.
devisha
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The following message was posted to: PharmPK
Dear all,
i would like to know as in this case in the other
period the volunteer consumed 230ml in period II , I
do agree that the variation in minimal however why
would a deviation be filled as there is a considerable
washout period that has elasped between the periods.
In case this is true that we need to analyse all the
calorie intake and other restrictions that need to be
abided by the subject in both the periods at least
till the period drug is not in its elimination phase
in the subject/volunteer.
In a simple BA/BE study the motto should be to keep
the variability between the subjects as low as
possible however in case it happens then the same
should be dealt on a case to case basis with adequate
reasoning.
Please correct me in case I am wrong.
thanks
kamakshi
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hi Kamakshi
I think you are writting about 240 mL of drinking water given with IP
administration.
If this is true.
Water is one of the factor that can affect the bioavailability of
drug. 10 mL deviation, it may or may not have significant impact on
the bioavailability of the drug that is depend on the physiology of
the subject.
If it may have significant impact on the bioavailability of the drug
than how can you justify without raw data. If you have filled
deviation for the same than you can justify.
There is no relation between 240 mL water and wash out period if you
give adequate wash out period.
In a simple BA/BE study the motto should be to keep standardization
within the subject in both the periods.
Best of my knowledge i had given above justification. May be there
is some addition or deletion.
Hope you understand me.
Virendra Patel
Alembic
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Why only 240ml of administered during bioequivalence estimation and
not any other volume?
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Dear Nirav,
This is the volume of Water specified by most of the guideline.
Also this volume of water is usually taken by the patients at the
time of taking medicine.
Regards:
Shaikh Feroz Ibrahim
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