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jag009 ★★★ NJ, 2012-05-04 01:00 (4812 d 19:53 ago) Posting: # 8510 Views: 11,081 |
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Hi everyone, Assuming a drug which is highly soluble and permable (BCS 1). The IR %release In-vitro is NLT 85% by 15-30 mins, yet the in-vivo Tmax is 4 hours (that's the minimum, some subjects have 10. Average is 6). Half-life of drug is 20-30 hours and it's ~ 85% protein bound. What factors contribute to ths long Tmax? Tissue distribution is obvious. Thanks John |
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luvblooms ★★ India, 2012-05-04 08:04 (4812 d 12:49 ago) @ jag009 Posting: # 8511 Views: 9,697 |
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Dear John One more reason could be hepatic recirculation helping in reaching Cmax (typical example: Raloxifene) Luv — ~A happy Soul~ |
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Chiku ☆ India, 2012-08-01 16:29 (4723 d 04:24 ago) @ luvblooms Posting: # 9015 Views: 9,383 |
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Raloxifene is class II drug with 4 % bioavailability and enterohepatic circulation may increase its bioavailability and may have impact on Cmax as well due to multiple peak phenamenon. Regards Chiku  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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Chiku ☆ India, 2012-08-01 16:26 (4723 d 04:27 ago) @ jag009 Posting: # 9014 Views: 9,391 |
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Dear John, Drug belongs to BCS class I that means it has good solubility and extent of absorption is comparable to IV. Tmax is indicator of rate of absorption so drug might be getting completely absorbed but rate can be slow that means long absorption half life. You can check Papp value and Maximum Absorbable Dose of that drug which might clear your doubt. There are no of BCS class I drugs having long Tmax such as mematanine. I hope it clears ur doubt. Regards Chiku |
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Helmut ★★★   Vienna, Austria, 2012-08-01 17:09 (4723 d 03:45 ago) @ Chiku Posting: # 9016 Views: 9,574 |
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Dear Chiku! ❝ There are no of BCS class I drugs having long Tmax such as mematanine. Not sure what you mean there. Memantine is BCS I (see also FDA’s guidance) with a long half life, but tmax (as expected) occurs early. We found the following (in hours): tmax (median, quartiles) t½ (xharm, ±SD)— 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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Chiku ☆ India, 2012-08-02 09:50 (4722 d 11:03 ago) @ Helmut Posting: # 9017 Views: 9,439 |
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Totally agreed with the data. We also got the same data. what i was trying to say is that Memantine being BCS I drug and low dose 10 mg IR tablet, is not rapidly absorbed (Tmax > 1.5 hr). It slowly absorbs in entire small intenstine and gives Tmax around distal ileum region. Off topic: why 36 subjects even 20 is suffecient. or you opted parallel design? Regards Chiku Edit: Full quote – once more – 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, 2012-08-02 21:57 (4721 d 22:56 ago) @ Chiku Posting: # 9027 Views: 9,438 |
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Hi Chiku! ❝ […] why 36 subjects even 20 is suffecient. or you opted parallel design? This was one of the design errors I made. See the entire story there. Based on the variability in the pilot study I didn’t want to run such a large large pivotal but the sponsor insisted in 36 subjects “just to be sure”. Given the shit happening afterwards he was right. P.S.: Pleeeze, don’t full quote like in all your previous replies in the Forum! The preferred style here is interleaved. [Helmut] — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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Chiku ☆ India, 2012-08-03 15:06 (4721 d 05:47 ago) @ Helmut Posting: # 9030 Views: 9,338 |
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Dear HS, Thanks for sharing that it is nice learning for me too. P.S.: sorry for inappropriate quoting of text. Regards Chiku:) |
Ing. Helmut Schütz