Compliance
★

India,
2016-02-11 09:02

Posting: # 15974
Views: 4,374

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
★★★

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

@ Compliance
Posting: # 15976
Views: 3,661

What ’bout science?

Hi Compliance,

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

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

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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Jay
☆

India,
2016-02-16 08:21

@ Helmut
Posting: # 15993
Views: 3,361

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
★★★

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

@ Jay
Posting: # 15995
Views: 3,373

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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