mmw
☆    

India,
2014-09-16 13:16
(3481 d 23:32 ago)

Posting: # 13518
Views: 4,812
 

 Steady state bioequivalence [Design Issues]

Dear all,

I have one query regarding steady state bio equivalence study of Tramadol SR 200 mg tablets.

In public assessment report of Tramadol in which post-dose 12 hours sample was taken on day 1 to 4.

link: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con140629.pdf

Also a bioequivalence study done in India; 12 hours post dose sample was collected on day 1 to 4. (Comparative bioequivalence studies of tramadol hydrochloride sustained-release 200 mg tablets - Accutest, India)

I want to know that what is significance of 12 hours post dose sample collection on day 1 to 4.

However guidelines states that “In multiple-dose studies, the pre-dose sample should be taken imme­di­ately before (within 5 min­utes) dosing and the last sample is recommended to be taken within 10 min­utes of the nominal time for the dosage interval to ensure an accurate determination of AUC(0–τ).”

I want to understand that why 12 hours post dose sample was collected from day 1 to 4.
nobody
nothing

2014-09-16 15:21
(3481 d 21:27 ago)

@ mmw
Posting: # 13521
Views: 3,847
 

 Steady state bioequivalence

❝ I want to understand that why 12 hours post dose sample was collected from day 1 to 4.


...to compare it to Ctau,ss from the EU MR guideline?

Kindest regards, nobody
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2014-09-16 15:27
(3481 d 21:21 ago)

@ mmw
Posting: # 13522
Views: 3,877
 

 Steady state bioequivalence

Hi mmw,

without knowing the studies’ protocols it is just guess-work. Sometimes studies contain a lot of exploratory stuff (mine do). The posology’s dosing interval is 12 hours (amazingly the PAR does not state the τ applied in the study). Maybe they were aware of the ongoing discussions of EMA’s MR-GL. Cτ in SD (here day 1) was suggested as a predictive metric of MD-performance. I was to lazy to check at which time-point they quantified Cmin on day 5 (I guess 24 hours post dose). C12 would be inter­esting as well, since this is the intended dosing interval.
BTW, why they sampled >24 hours in steady state is beyond my intellectual reach.

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
jag009
★★★

NJ,
2014-09-16 18:34
(3481 d 18:14 ago)

@ Helmut
Posting: # 13524
Views: 3,915
 

 Steady state bioequivalence

Hi Helmut,

❝ BTW, why they sampled >24 hours in steady state is beyond my intellectual reach.


Some sample > 24 hrs to capture the half-life, yes the half-life at steady state. I know some old timers and they like running steady state studies with the sampling time pts beyond the dosing interval so to obtain the half-life, for NDA purpose.

John
UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
95 visitors (0 registered, 95 guests [including 9 identified bots]).
Forum time: 11:48 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