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Back to the forum  Query: 2017-11-24 14:01 CET (UTC+1h)

Truncted AUC, low variability [Design Issues]

posted by Helmut Homepage - Vienna, Austria, 2017-08-16 14:18  - Posting: # 17693
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Hi ssussu,

which is your “target” agency? If you want to submit the study to the (US)FDA you have to provide the protocol to the OGD for review anyway.
BTW, I never understood why the FDA allows AUC0–72 for drugs with “low intrasubject variability in distribution and clearance only. The latter might be possible to show based on published data (though difficult because one needs the subjects’ λz). The former is almost impossible without raw data and PK modeling. In BE we are interested in absorption (property of both the drug and the formulation). Distribution/elimination are solely properties of the drug. I don’t get the FDA’s rationale.

» If I just sampling for 72hr, how can I prove the drug is a long half life drug?

I agree with what ElMaestro wrote. You posted in the right category – that’s a design issue. Think about planing the washout. It is based on an expected half-life (literature, previous studies). No agency* asks for a demonstration that f.i. the washout was 5–10×t½ of subjects (only that there are no residual concentrations >5% of Cmax in higher periods).

It is an open question what a “long half-life drug” is. An numerous conferences both the FDA and the EMA refused to give a definition. Only the Canadian HPFB formerly stated t½ ≥24 hours.

Helmut Schütz 

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