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joyjac ★ Philippines, 2012-05-15 11:22 (5139 d 20:34 ago) Posting: # 8570 Views: 13,658 |
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Dear colleagues, While literature indicates that omeprazole is a highly variable drug, can anyone help me know the range of CVs (minimum, maximum) for Cmax, AUC0-t and AUC0-inf, particularly, for the comparator/innovator drug, Losec? Supposing omeprazole is combined with an anti-inflammatory drug i.e. naproxen, will the variablity of omeprazole be reduced? What would be the best design for such fixed dose combination? Thank you for the kind help. |
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drgunasakaran1 ★★  2012-05-15 11:50 (5139 d 20:06 ago) @ joyjac Posting: # 8571 Views: 12,331 |
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Dear Mr Joyjac, You can find the Intrasubject variability of Omeprazole in the following Public Assessment Reports. Public Assessment Report 1 Omeprazol “Copyfarm” Omeprazole Public Assessment Report 2 Omeprazole Bentley 10mg, 20 mg and 40 mg capsules Public Assessment Report 3 UK/H/1024/001-003/DC Sandoz Omeprazole — Dr Gunasakaran Sambandan MD Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn |
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Helmut ★★★   Vienna, Austria, 2012-05-15 21:00 (5139 d 10:56 ago) @ drgunasakaran1 Posting: # 8572 Views: 12,099 |
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Dear Dr. Gunarsakaran, THX for digging out these PARs. Always interesting reading matter.  ❝ Public Assessment Report 1 Omeprazol “Copyfarm” Omeprazole “The primary pharmacokinetic variables evaluated for single dose studies were AUC0-t and Cmax and for steady state, AUCτ and Cmax. Bioequivalence was determined based on limits of 80-125% for AUC and 70-143% for Cmax. Based on the pharmacokinetic parameters of omeprazole, it can be concluded that Omeprazol “Copyfarm” and Losec/Antra tablets from AstraZeneca are bioequivalent with respect to rate and extent of absorption, and fulfil the bioequivalence requirements outlined in the relevant CHMP Note for Guidance.” (my emphasis) The 2001 NfG stated: In certain cases a wider interval may be acceptable. The interval must be prospectively defined e.g. 0.75-1.33 and justified addressing in particular any safety or efficacy concerns for patients switched between formulations. (my emphasis again)The 2006 Q&A document stated: The possibility offered here by the guideline to widen the acceptance range of 0.80 – 1.25 for the ratio of Cmax (not for AUC) should be considered exceptional and limited to a small widening (0.75 − 1.33). … applicable only if CVWR >30% was demonstrated in a replicate design study.The upper CLs of Cmax were 137% (10mg, fasting, MD), 142% (20mg, fed, SD), 135% (20mg, fasting, MD). It’s good to see that – even in Denmark – assessors didn’t take guidelines literally.* BTW, in the only replicate design study (20mg, fasting, SD) CVintra of Cmax was 45%.
— 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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pash413 ★ India, 2012-12-06 19:09 (4934 d 11:47 ago) @ Helmut Posting: # 9685 Views: 11,324 |
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Dear all One small confusion how to control last point Cmax in Fed BE study of prazole DR tablets. In some subjects Cmax is observed in last time points. Shall we exclude data of such subjects from final BE calculation? |
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Helmut ★★★ Vienna, Austria, 2012-12-07 16:29 (4933 d 14:27 ago) @ pash413 Posting: # 9689 Views: 11,368 |
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Dear Pash! ❝ One small confusion how to control last point Cmax in Fed BE study of prazole DR tablets. In some subjects Cmax is observed in last time points. What was your sampling schedule? Did these subjects show low concentrations as well? Did you observe this effect both after test and reference or only after the reference? See this nasty example. ❝ Shall we exclude data of such subjects from final BE calculation? What do you mean by “shall we”? What does your protocol state? To which regulatory agency will you submit the study? — 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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wienui ★ Germany/Oman, 2016-04-07 13:00 (3716 d 18:56 ago) @ Helmut Posting: # 16169 Views: 8,971 |
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❝ ❝ “The primary pharmacokinetic variables evaluated for single dose studies were AUC0-t and Cmax and for steady state, AUCτ and Cmax. Bioequivalence was determined based on limits of 80-125% for AUC and 70-143% for Cmax.” Dear All, Could we widen the Cmax rang to 70-143% of HVD (Omeprazole) in a normal (not a replicate) 2x2 crossover BE study. Thanks, — Cheers, Osama |
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Helmut ★★★ Vienna, Austria, 2016-04-07 14:57 (3716 d 16:59 ago) @ wienui Posting: # 16170 Views: 8,937 |
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Hi wienui, ❝ Could we widen the Cmax rang to 70-143% of HVD (Omeprazole) in a normal (not a replicate) 2x2 crossover BE study. Regulatory perspective: According to all current guidelines I am aware of, no. Scientific perspective: Why not? Omeprazole formulations are already OTC in many countries. Hence, the efficacy/safety profile is established. Many other products were approved with an AR of 70–143% in 2×2 studies in the EU (was recommended as the standard [sic] for Cmax in the 9th draft of the NfG1 following suggestions of Blume et al.2). Following the concept of reference-scaling one has to demonstrate that the reference in the particular study shows a CV of >30%. Given the data in the public domain I would say we can be pretty sure that the reference is a HVDP indeed. Just my two cents.
— 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 |
Ing. Helmut Schütz