Compliance
★    

India,
2016-02-11 09:02

Posting: # 15974
Views: 4,322
 

 How to decide partial AUC [NCA / SHAM]

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]
Helmut
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Vienna, Austria,
2016-02-11 17:43

@ Compliance
Posting: # 15976
Views: 3,611
 

 What ’bout science?

Hi Compliance,

» Please teach me how to decide/ fix partial AUC regimen.

[image]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.

Cheers,
Helmut Schütz
[image]

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Jay
☆    

India,
2016-02-16 08:21

@ Helmut
Posting: # 15993
Views: 3,309
 

 What ’bout science?

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
Helmut
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Vienna, Austria,
2016-02-16 13:12

@ Jay
Posting: # 15995
Views: 3,321
 

 What ’bout science?

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–τ
  2.0         44.4%          55.6%
  1.0         38.0%          62.0%  ⇐ flip-flop
  0.5         34.3%          65.7%

Reminds 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.

Cheers,
Helmut Schütz
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