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In BA/BE studies if two peaks appear in plasma time curve which
should be considered as a cmax. Is there any supporting guideline
which describe in detail this problem.
With Regards
Anuj Saini
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The following message was posted to: PharmPK
Dear Anuj,
In noncompartmental analysis, Cmax is the Maximal Observed
Concentration; it does not matter if it is the first or the second peak.
Regards,
Jean
[Could it be the average? - db]
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Could it be the average?
If it is submitted to the FDA, I would say no. In the FDA guidance
(http://www.fda.gov/CDER/GUIDANCE/5356fnl.pdf) on page 12 it is written
the following:
"We recommend that peak exposure be assessed by measuring the peak drug
concentration (Cmax) obtained directly from the data without
interpolation."
Jean
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Dear Jean, two peaks in a PK study? Doesn't this imply enterohepatic
circulation of the compound? And can noncompartemental analysis still
be used then? Without knowing the data I would recommend to repeat
the study with at least triplicates for every timepoint to see if the
two peaks are consistend throughout the studies.
regards
Matthias
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The following message was posted to: PharmPK
Matthias,
The question was in the context of BA/BE study and the goal is to
compare the rate and extend of absorption between a test and a reference
formulation. Usually these types of PK studies are performed by using
noncompartmental methods and submitted to regulatory agency.
If 2 peaks are observed, it could be because the medications are
modified release or sustain release. It does not necessary imply
enterohepatic circulation, but it could be possible. In order to use
noncompartmental analysis, linear kinetic is assumed. The PK of the
reference compound should be known up front. With these information the
generic company should know if they can use or not the noncompartmental
analysis.
Regards,
Jean
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The following message was posted to: PharmPK
Dear Matthias,
You are correct, this molecule is well known for enterohepatic
recirculation. Does it require compartmental analysis for USFDA
bioequivalence study?
With Regards
Anuj Saini
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Dear Matthias,
There could be hundreds of reasons for multiple peaks.
If your analytical method ensures proper validation then go ahead
considering the highest conc. as Cmax.
But, there are chnaces that you may end up with lots of AUCinf values
missing.
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