Bioequivalence and Bioavailability Forum

Dear Claire

❝ If a compound is known to display a first peak around 5 hours and a second one around 12 hours,

Now one Question: Whether the first peak is prominent or second peak?

❝ do you think a study ought to include intensive sampling to characterize the second peak as well as the first?

Ans: If second peak is because of hepatic recirculation, IMHO you will not be able to do anything. But if the double peaks appear because of pH solubility profile (eg. Diclofenac) then you should try to capture both as they are interdependent.

Ref:
1) http://www.ncbi.nlm.nih.gov/pubmed/11097147
2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675780/
3) http://deepblue.lib.umich.edu/bitstream/2027.42/34601/1/83_ftp.pdf

❝ The guidelines don't seem to mention this and I haven't come across mention of this topic on this forum. It seems that most of the time, a second peak is not expected, or the reasons for it are unclear, but when it is expected...?

Double peak absorption has been described with several orally administered drugs. Numerous reasons have been implicated in causing the double peak Examples:
a) http://dmd.aspetjournals.org/content/27/8/855.full#ref-7
b) http://www.ncbi.nlm.nih.gov/pubmed/20381191
c) http://www.omicsonline.org/0975-0851/JBB-03-101.php
d) http://onlinelibrary.wiley.com/doi/10.1002/bdd.492/abstract
e) http://www.ncbi.nlm.nih.gov/pubmed/3694496
f) Differential absorption
Hope this will help!!!


Regards

Luv!!

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Edit: Standard quotes restored. [Helmut]