Bi-/multi­phasic MR Pro­ducts – EMA MR-Guide­line [NCA / SHAM]

posted by beman – 2015-10-19 14:31 (3083 d 23:38 ago) – Posting: # 15571
Views: 5,262

Dear all,

in the new EMA-modified release guideline is stated, that for all phases partial AUC's, Cmax and tmax should be calculated. The time point for truncationing should be based on the PK-Profile and should be specified in the study protocol.

Considering following biphasic-case (biphasic tablet and biphasic PK-Profiles):
peak 1 (first tmax) around 2 hours, peak 2 about 6 hours, local minimum about 4 hours.

First, there are two possible cut-off time points:
- 2 h (as early exposure - FDA)
- 4 h (for separating the two phases as shown in the profile)

In my Opinion the 4 h as cutoff time-point is the right one, because it is - in contrast to an 2 h cutt-off time point - possible to determine the first Cmax appropriately.

Second, there are two different ways to define the Cmax of the phases (cutoff is 4 h, next blood sampling time point 4.5h) in accordance to the guideline :
- Cmax(0-4h) and Cmax(4h - t)
- Cmax(0-4h) and Cmax (4.5h - t)

If the profiles are 'as expected', the results are of the two approaches are the same. But if there are some 'not expected' profiles (for example only one peak), Cmax(0-4h) and Cmax(4h - t)could be the same (4h-)value.

From scientific point of view, i would prefer: Cmax(0-4h) and Cmax (4.5h - t). But in studies i would prefer the other approach.

What is your opinion to these issues ?

Best regard

BEman


Edit: Category changed. [Helmut]

Complete thread:

UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
102 visitors (0 registered, 102 guests [including 7 identified bots]).
Forum time: 13:09 CET (Europe/Vienna)

With four parameters I can fit an elephant,
and with five I can make him wiggle his trunk.    John von Neumann

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5