What is clinically relevant? [Design Issues]

posted by Helmut Homepage – Vienna, Austria, 2018-04-04 16:49 (1596 d 02:20 ago) – Posting: # 18641
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Hi BF,

» A mix of liposomal-bound and free doxorubicin is infused, …

Are you sure? I know only liposome-encapsulated formulations (i.e., containing no free doxorubicin).

I agree that the FDA’s guidance (asking for AUC and Cmax of free and liposome-encapsulated doxorubicin) might not sufficiently enough characterize the profiles.

There is no product-specific guidance in Europe so far. However, current regulatory practice on this side of the pond is much more strict.
PK metrics for encapsulated, free, and total doxorubicin:PK metrics for the primary metabolite doxorubicinol: As above but supportive only.

Problems are manifold:IMHO, encapsulated and total doxorubicin are not relevant from a clinical perspective – only nice to know. I would prefer to assess just the metabolite but all of its PK metrics in a confirmatory manner.

BTW, at the 3rd GBHI conference (Amsterdam, April 12–13) Session IV will be devoted to liposomal parenteral preparations. Let’s wait for regulators’ unfathomable wisdom.

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