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jag009 ★★★ NJ, 2017-09-06 23:11 (2415 d 22:03 ago) Posting: # 17787 Views: 5,449 |
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Hi guys(and girls), What is your opinion on this guidance about BE needs to be demonstrated for 2 active metabolites and not the parent? They want all three measured too. The parent is rapidly absorbed from a 600mg dose, with a peak plasma concentration of 1.98 mg/l occurring approximately 90 minutes after ingestion. The absolute bioavailability of a 20 mg oral dose is 69%. The parent is primarily via pathways involving N-demethylation and terminal hydroxylation... In vitro studies have shown that CYP450 3A4 is primarily responsible for the metabolism.... I don't get it. The message has always been (or almost always been) to show BE for parent if it can be accurately quantified since it is the one that gets absorbed. Someone was  when the document was written?J |
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ElMaestro ★★★ Denmark, 2017-09-07 00:52 (2415 d 20:23 ago) @ jag009 Posting: # 17788 Views: 4,664 |
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Hi Jag, ❝ I don't get it. The message has always been (or almost always been) to show BE for parent if it can be accurately quantified since it is the one that gets absorbed. Someone was I agree this is unusual. I don't know if they were partying too hard when they wrote this guideline but I can easily imagine there is a compromise of sorts involved here; perhaps someone from another FDA office (DBRUP?) wasn't convinced or was inexperienced with BE and used intuition instead of reason? Sometimes these guidelines, even though they are issued by OGD, involve a ton of inter-division compromises. I am sure that unless you find a really good reason buried in the material on the originator available via FOI the reason is going to be very hard to identify.  We all have to be sheep in this situation, I guess.  — Pass or fail! ElMaestro |
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yicaoting ★ NanKing, China, 2017-09-07 04:32 (2415 d 16:42 ago) @ ElMaestro Posting: # 17789 Views: 4,683 |
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❝ ❝ We all have to be sheep in this situation, I guess. Wow, a pack of wolves is coming....  |
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jag009 ★★★ NJ, 2017-09-07 08:16 (2415 d 12:58 ago) @ ElMaestro Posting: # 17790 Views: 4,596 |
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Hi ElMaestro, ❝ Hi Jag,I am sure that unless you find a really good reason buried in the material on the originator available via FOI the reason is going to be very hard to identify. Even in the NDA the levels of all three analyte plus another metabolite (which FDA doesn't want to see) were reported... Oh well... J |
Ing. Helmut Schütz