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Jana Zigova ☆ Slovakia, 2015-02-10 10:34 (4151 d 12:01 ago) Posting: # 14394 Views: 6,591 |
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Dear forum members, I would appreciate your opinion regarding following query: Current EU guideline on BE discourages from the use of a metabolite as a surrogate for parent compound, pointing it can be accepted only exceptionally. This might be the case of Diosmin products for which determination of Diosmin in human plasma is impossible. Even the determination of Diosmin’s aglicon – free Diosmetin – has proven to be difficult due to its low concentrations, for most of Diosmetin is present in the blood as glucuronide. The solution might be represented by enzymatic degradation of plasma samples applied to conjugated Diosmetin. I am just wondering whether this kind of surrogate – free Diosmetin obtained after enzymatic degradation – can be viewed as the acceptable one. Looking forward to your view! Jana |
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Helmut ★★★   Vienna, Austria, 2015-02-10 13:18 (4151 d 09:17 ago) @ Jana Zigova Posting: # 14396 Views: 4,471 |
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Hi Jana, ❝ Current EU guideline on BE discourages from the use of a metabolite as a surrogate for parent compound, pointing it can be accepted only exceptionally. Correct. The further down you walk the metabolic chain the more difficult it will be to convince regulators that a metabolite is sensitive enough to reflect potential differences in formulations. In a linear PK system differences in AUC are expected to be carried over, but differences in Cmax diminish. You have to show reliable data supporting your claim that “determination in plasma is impossible”. Referring to a paper in an obscure journal is definitely not sufficient. I would suggest a scientific advice at a “difficult agency“. Two years ago the Spanish agency accepted our suggestion of a secondary (!) metabolite to show BE. We presented a lot of bioanalytical data and the results of pilot study… Good luck. — 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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Jana Zigova ☆ Slovakia, 2015-02-12 09:12 (4149 d 13:24 ago) @ Helmut Posting: # 14410 Views: 4,296 |
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Hello Helmut, Thank for your judgement as well as boost! Jana |
Ing. Helmut Schütz