Log in
Register|
CLR ☆ Singapore, 2012-04-18 08:35 (5186 d 03:46 ago) Posting: # 8439 Views: 4,873 |
|
|
Dear all, If a compound is known to display a first peak around 5 hours and a second one around 12 hours, do you think a study ought to include intensive sampling to characterise the second peak as well as the first? 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...? Thanks, Clare |
|
luvblooms ★★ India, 2012-04-18 15:41 (5185 d 20:41 ago) @ CLR Posting: # 8440 Views: 4,112 |
|
|
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!! Edit: Standard quotes restored. [Helmut] — ~A happy Soul~ |
|
CLR ☆ Singapore, 2012-04-23 08:21 (5181 d 04:01 ago) @ luvblooms Posting: # 8454 Views: 3,942 |
|
|
Dear Luv (how affectionate  ),Thanks for this. In my particular case, enterohepatic recirculation has been proposed as a possible reason for the appearance of the second peak. The first peak is the prominent one though. In the cases I've come across, we don't see many where there is some indication that the double peaks appear consistently among all the subjects recruited to the study, and I was just wondering how vital it is to make sure the sampling times are there to capture this second peak. Regards, Clare |
|
Chiku ☆ India, 2012-08-03 15:52 (5078 d 20:30 ago) @ CLR Posting: # 9031 Views: 3,784 |
|
|
In my opinion it is extremely vital to characterize the second peak especially for BE study with NCA of Pharmacokinetics. we had a recent set back of MR product where double peaks were observed but due to non charecterization of second peak (less sampling time point) Cmax was bioequivalent ~90 % and AUC was no ~40 %. there were other reasons as well but sampling time points was major reason. I would say if second peak is due to formulation characteristics and it is variable i.e wide range of magnitude of second peak then for BE study it is vital atleast for AUC. Although there can be number of categories the second peak can come such as multiple peak phenmenon due to physiological reason, MR formulation such as IR +DR, DR+ER, MMX etc. So careful evaluation of second peak is imp. Regards Chiku:) |
Ing. Helmut Schütz