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The following message was posted to: PharmPK
Dear Colleagues,
A pleasant day to you all!
We are planning to do a bioequivalence study on a modified release
preparation (MR) administered once a day versus an immediate release
(IR)
dosage form given twice a day. The study design will be that of a
multiple
steady state and blood sampling will be based on the half-life of the MR
product rather on the inherent IR drug product's half-life. However,
there are no published data on the half-life of the MR . The half-life
of
the IR product is reported to be in the range or 3-6 hours (although
some
investigators reported the half-life to be in the range of 2-4 hours).
Any advice on how many days are we going to administer the dose? Also,
can
you please educate me on what a flip-flop phenomenom means? Any
references?
Thank you for your kind attention.
Jocelyn L. Jacob
Mandaluyong City
Philippines
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The following message was posted to: PharmPK
Dear Jocelyn L. Jacob,
Normally steady state is attained in five biological half lives but
in this case you are comparing the Once daily MR with IR BD dosing so
you need to continue dosing till five dosing intervals of MR to
evaluate the steady state parameters.
Flip Flop with reference to the Pharmacokinetics means "a phenomenon
where we observe Elimination rate of the drug is fater than absorption
rate all through .Metformin Hydrochloride is a classical example of
drug having Flip Flop kinetics.
Flip Flop with reference to the drug release profile through a
monolithic device ( Matrix ) is quantitatively slower release at the
distal ( latter) part of release curve.This is a common phenomenon with
the High Molecular weight Hydrophillic Swellable matrix releasing with
first order or near kinetics wherein initially we get linear release
with time and at latter ( say after 60 to 70%)there is a flip flop
phenomenon ( Sudden tail off in release)as the diffusion path for the
drug to traverse increases due to matrix swelling.
I hope this makes sense,
Kind Regards ,
Pradeep Bhadauria
RANBAXY RESEARCH LABORATORIES.
INDIA.
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Hi Jacob
Well you will have to do a pilot study to determine the t1/2 of your MR
formulation. Theoretically it will not
make any difference whether you use reference or test products half
life to select the time points. this is
because as long as primary criteria for bioequivalence are met (i.e.
ratios and CI for Cmax, AUC and AUC inf),
and you have GCP compliance, no regulatory authority would be expected
to bother about some scientific
liberty like one you have proposed.
I have a question - what is the advantage you are looking at,
especially when you do not have the information
you propose to use?
IMHO it is better to use the standard products half life for selection
of time points.
About your other queries - they have been addressed by other members
already.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)