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The following message was posted to: PharmPK
I wish to design a protocol for multiple dose bioequivalence
study on fluoxetine. This would be an Europian submission.
The regulatory body has asked to do a multiple dose study
considering both the parent drug and the metabolite, nor
fluoxetine for BE criteria.
What I undestand for multiple dose study is that one has to
repeat a drug at an interval equal to its half life. Usually
this is done for 5-7 administrations so that a steady state
is achieved. Before every dosing we need to take a blood
sample for drug quantification. The steady state's arrival
can be confirmed from these time points. During the last
drug administration, the sampling points are placed on the
absorption/elimination phases as usual and usually is
extended to cover three half lives post to last dose.
For fluoxetine the following things are really confusing me.
1) What should be the dosing interval? Should it
be with reference to the parent drug, or metabolite or both
of them? (We are going to apply the BE criteria to both of
2) A dosing done on daily basis will not give a real steady
state picture. For that we must have dosing at the end of
3) The elimination half lives are 4-5 days and 5-15 days for
the parent drug and the metabolite respectively. How to
address this issue in the study protocol? (eg washout
period, sampling points etc)
4) Considering the long half lives, can't we go for a
parallel design here?
I searched on net extensively but it was fruitless.
Requesting you to comment.
Regards and thanks in advance,
Dr Suhas Khandave
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