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Compliance ★ India, 2016-02-11 10:02 (2987 d 00:34 ago) Posting: # 15974 Views: 6,335 |
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Dear All, Please teach me how to decide/ fix partial AUC regimen. Europe guidance for modified release formulation ask for the partial AUC but i don't have knowledge how to select regimen for partial AUC. Regards, Compliance Edit: Category changed. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2016-02-11 18:43 (2986 d 15:53 ago) @ Compliance Posting: # 15976 Views: 5,272 |
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Hi Compliance, ❝ Please teach me how to decide/ fix partial AUC regimen. ![[image]](img/uploaded/image77.jpg) Impossible without a crystal ball. You should know the PK/PD of the API and the properties of the formulation.❝ Europe guidance for modified release formulation ask for the partial AUC but i don't have knowledge how to select regimen for partial AUC. The GL states: An early partialAUC(0 – cut-off t) and a terminal partialAUC(cut-off t - tlast), separated by a predefined cut-off time point, e.g. the half of the dosage interval are recommended, unless otherwise scientifically justified. In other words, if you have no clue you could always use τ/2. For some formulations (e.g., biphasic release) such a cut-off is meaningless and IMHO, for the others of doubtful value. I cannot imagine a situation where I would ever use it myself. That’s why the second option was added in the final version. Up to you.— 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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Jay ☆ India, 2016-02-16 09:21 (2982 d 01:15 ago) @ Helmut Posting: # 15993 Views: 4,862 |
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Hi, As mentioned in the EU GL, half of dosage interval may be considered. So if the label states once a day then AUC0-12 and AUC12-last may be considered. Regards, Jay |
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Helmut ★★★ Vienna, Austria, 2016-02-16 14:12 (2981 d 20:24 ago) @ Jay Posting: # 15995 Views: 4,890 |
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Hi Jay, ❝ As mentioned in the EU GL, half of dosage interval may be considered. So if the label states once a day then AUC0-12 and AUC12-last may be considered. Thank you for repeating what I already have written above. Do you have an own opinion? I don’t see any pharmacokinetic justification for a cut-off of τ/2 but I’m always eager to learn something new. I can only speculate that the idea of the almighty oracle was to catch with the partial AUCs 50% of the AUC0–τ but that doesn’t work: kabs/kel AUC0–τ/2/AUC0–τ AUCτ/2–τ/AUC0–τReminds me on an innovator (!) company which had the splendid idea to develop a new formulation of an antibiotic (doubled strength) in order to “double the time above the MIC”. When I talked about first-order processes and exponential functions and that therefore, this concept could never work they didn’t believe me at first. When I presented some plots they trashed the project. Lack of basic PK knowledge is abundant. — 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