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cakhatri ★ India, 2012-09-07 07:58 (4628 d 08:51 ago) Posting: # 9157 Views: 10,592 |
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Dear Members, Thanks to the forum for accepting me as a member and the registration process was indeed very quick. I would appreciate your views on a situation like For one of the pilot studies on Metaxalone in Fed conditions versus Ref (Skelaxin) 800mg, for 50% of the volunteers we have observed steep increase in concentration at 16th and 24th hour timepoints (last sample at 72hrs) for both test as well as Ref product.16th and 24th hour samples were collected in-house All the volunteers had consumed fed breakfast and nothing was leftover. Such observations are very rare unless the product is known to be having two absorption phases (e.g Dexlansoprazole), but nothing reported for Metaxalone. From the analytical perspective the samples were repeated and found to have similar concentration. There was no mixup of the samples between volunteers at 16th and 24th hour. Anything from formulation and or pharmacology perspective would help Regards Chirag Edit: Category changed. [Helmut] |
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jag009 ★★★ NJ, 2012-09-08 01:20 (4627 d 15:28 ago) @ cakhatri Posting: # 9161 Views: 9,105 |
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Hi Chirag, I have the same observations before and believe it was due to enterohepatic recirculation. There is an article somewhere which talked about this. John |
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cakhatri ★ India, 2012-09-08 08:08 (4627 d 08:41 ago) @ jag009 Posting: # 9162 Views: 9,071 |
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Hi John, Thanks for the information, i tried searching for specific article on metaxolone with such situation but couldnt find one, is it possible for you to provide link and advise what measures to take to avoid such situation Regards Chirag Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] |
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Helmut ★★★   Vienna, Austria, 2012-09-08 14:29 (4627 d 02:20 ago) @ cakhatri Posting: # 9164 Views: 9,363 |
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Hi Chirag! ❝ […] advise what measures to take to avoid such situation Generally enterohepatic recirculation is a property of the drug – not of the formulation. In BE we are only interested in the latter. If you suspect recirculation you can opt for AUC72 thus avoiding potential problems in estimating the elimination phase (which might be your case). Since the study is already finished you can only discuss the results and concentrate on AUC72 rather than on AUCt/AUC∞. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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cakhatri ★ India, 2012-09-11 08:26 (4624 d 08:22 ago) @ Helmut Posting: # 9172 Views: 9,032 |
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Dear Helmut, Thanks for your suggestion. The situation is
Regards Chirag Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Jaime] |
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jag009 ★★★ NJ, 2012-09-13 21:56 (4621 d 18:53 ago) @ cakhatri Posting: # 9209 Views: 9,067 |
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Hi Chirage, ❝ carried out a pilot study and there was no such observation. Not surprise. Some studies of mine had > 60% of the subject with Tmax > 14 hrs while others had like 1 or 2 subjects. ❝ The last sample is at 72hrs, the observation of double absorption is seen from 16th hour onwards (Cmax) and in some cases 24hrs also (Cmax) and therefore AUC estimates are not reliable You mean AUCinfinity? For subjects who exhibit the late Tmax, do they show a peak at (e.g.) Tmax > 14 hours for both treatments? John |
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jag009 ★★★ NJ, 2012-09-11 00:30 (4624 d 16:18 ago) @ cakhatri Posting: # 9168 Views: 9,049 |
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Hi Chirag, The article is not specific for Metaxalone but for drugs that exhibit enteroheptic recirculation. I see if I can find the bibliography. Like Helmut said, it shouldn't really be a problem for BE evaluation unless Cmax happens to occur at that timepoint (16 or 24?). John |
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cakhatri ★ India, 2012-09-11 08:29 (4624 d 08:20 ago) @ jag009 Posting: # 9173 Views: 9,048 |
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Hi John, Thanks for the reply, as I said in my reply to Helmut, the double absorption at 16 and 24 hrs accounts to Cmax Regards Chirag Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Jaime] |
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Chiku ☆ India, 2012-09-14 08:30 (4621 d 08:19 ago) @ cakhatri Posting: # 9210 Views: 8,930 |
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Hiii U can calculate elimination rate for both the peaks if it is same then it is formulation related peak. As enterohepatic circulation tend to change half life of the molecule. This very rough understanding but still will help. Regards Chiku:) |
Ing. Helmut Schütz