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"Is there any guide line from UK / EU which accepts the bio equivalence
of
the product based on
Cmax ( 75 -133 %)
AUC (80 - 120 %)
If yes can any one please suggest me the reference ?
Dr. Mahesh Samarth
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The following message was posted to: PharmPK
hello Mashesh,
I suggest that you visit the FDA website in which you will find the
guidance for bioequivalence.
I don't have the link here but you should find this easily in the
website as there is a search by keyword module as I remember.
Hope this helps,
Regards
Frederic Doc
PFIZER Global R&D
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Dear Mahesh:
The European Agency has a guideline "Note for guidance on the
investigation
of BA and BE" from July 2001 (is my version):
http:\\www.eudra.org\emea.html
Have a look to it,
Regards,
Silvia
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The following message was posted to: PharmPK
Dear Mahesh,
you will find the current EU guideline at
http://www.emea.eu.int/pdfs/human/ewp/140198en.pdf
see page 11: 3.6.2. Acceptance range for pharmacokinetic parameters
AUC-ratio
The 90% confidence interval of this measure of relative bioavailability
should lie within an acceptance range of 0.80-1.25. In specific cases
of a narrow therapeutic range the acceptance interval may need to be
tightened.
In rare cases a wider acceptance range may be acceptable if it based on
sound clinical justification.
Cmax-ratio
The 90% confidence interval of this measure of relative bioavailability
should lie within an acceptance range of 0.80-1.25. In specific cases
of a narrow therapeutic range the acceptance interval may need to be
tightened.
In certain cases a wider interval may be acceptable. The interval must
be prospectively defined e.g. 0.75-1.33 and justified addressing in
particular any safety or efficacy concerns for patients switched
between formulations.
According to my experience (500 BA/BE studies) it is not a bad idea to
read the second paragraph for Cmax over and over again. There is
nothing like "Cmax in the EU within 0.75-1.33" (or even 0.70-1.43 as
stated in an early draft of the guideline). If you want to go for the
MRP (Mutual Recognition Procedure) it is also not a bad idea to contact
the healthy authority of the country of your choice (which will act as
the "referrer" within the EU) in the planning phase of the study.
Good luck
Helmut
P.S. I would not suggest to visit the FDA website in search of EU
guidelines ;-)
Helmut Schütz Biokinet GmbH / Dept Biostatistics
Neubaugasse 36/11 Nattergasse 4
A-1070 Vienna/Austria A-1170 Vienna/Austria
tel/fax +43 1 9713935 tel +43 1 4856969 62
no cell phone ;-) fax +43 1 4856969 90
http://www.goldmark.org/netrants/no-word/attach.html
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Dear friends
I want to know how to carryout the bioequivalence
study of doxazocin, 8 mg modified release formulation.
For doxazosin, postural hypotension and first dose
syncope are the major side-effects with the first high
dose and for doxazosin it is recommended that the
treatment is initiated with the 1 mg dose and dose
should then be increased to 2, 4 and 8 mg to the
required high dose.
But i can't titrate the dose in a bioequivalence
study. So, whats the way out...
Is it acceptable to carryout the bioequivalence at
lower dose and ask for waiver at higher dose.
Any suggestions and references are highly appreciated,
Thanks in advance,
Jayasagar
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The following message was posted to: PharmPK
Dear Jayasagar,
It is very much possible to get bio-waivers on higher strengths in
selected products wherein the safety of healthy volunteers at higher
doses is at stake. You may refer to the BA-BE guidance issued by the US
FDA, for the same.
Moreover the FDA requires that the BE must be established against the
RLD (Reference Listed Drug) and for Doxazosin IR formulation, I think,
the RLD mentioned in the orange book is 1 mg.
I hope this will help.
Regards,
Hitesh Maheshwari
Astron Research, India
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Well Sagar
The side effect of p[ostural hypotension is very common and well
documented for doxazocine. But it can be avoided if during meaurement
of BP, the volunteers are made to sit for 2 minutes and then made to
stand up for measurement of Blood pressure.
I think this can substantially reduce the risk of postural
hyo\potension and moreover, the 8 mg dose mentioned by u is quite high.
Regards
Tausif ahmed
Dept. of Pharmaceutical Medicine
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