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It is with respect to the BE study where i have got the AUC%
extrapolated more than 20% in some subject, let me know how to
proceed for the calculation of the AUCinf.
Thanks,
Ratnakar jadhav
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Dear Ratnakar,
Generally as per guidelines, AUC0-t should be above 80%. For that
reason we
have to take sampling points upto minimum three half lives. For three
half
lives about 87% will be eliminated from the body.
AUCinf can be calculated using the following formula,
C*
AUCinf = AUC0-t + ---
Kel
C* = Concentration measured at last time point
Kel = Elimination rate constant.
AUC0-t can be calculated from Trapezoidal rule.
AUCinf will be depend up on Kel. If Kel increases AUCinf will decreases.
regards,
Srinivasa Reddy.E
Research Analyst
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The following message was posted to: PharmPK
Dear Mr Rtanakar Jadhav,
The AUCinf will be calculated similarly as of other subjects. This
may result in getting shorter half lifes in those subjects which may
differ from the other subjects. This happens mainly because of the
low sensitivity of the method or due to the biphasic elimination
patern of the drug molecule.
Regards
Manoj K V
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Dear Srinivasa,
Thanks for your prompt reply, actually the AUC% extrapolated is found
more
than 20% in some subject is due to the large variation in the half-
life what
we have got wrt the reported one. Now the querry is that should we delet
these subjects from the calculation of AUCinf or we can include them, as
drug is passinng the Conventinal Bioequivalence Criteria of 80-125%
for all
(e.g. Cmax, AUCt & AUCinf) after inclusion of these subjects. Or
tommorow
there should not be any issue regarding the inclusion of these
subjects who
have AUC% extrapolated more than 20%. Is it mandatory that the AUC%
extrapolated 20% always should be less than 20%, If yes which
guidlines, do
you have any other alternative solution for the same.
Thanks
Ratnakar jadhav
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The following message was posted to: PharmPK
Dear Mr Ratnakar,
As per the response of Dr Srinivas AUC inf is to be calculated as
per the equation mentioned in his answer , it is also recommended to
mention in the protocol how you will be calculating the Kel (e.g of
No .of points and the regression value).
You can not delete any subject from the study unless you prove them
outlier upon suitable statistical analysis.
As you said the study is meeting the BE creteria and power with
respect to all the parameter Cmax ,AUCo-t & AUCinf ,I hope the study
is clear since you reporting an average BE study not an individual BE
study.It is desirable that the AUC% extrapolated should be less than
20%, but this had happened in few subjects which could be due to the
individual response. Please refer US FDA guidance on BA/BE studies.
Regards
Manoj K Vishwakarma
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