yoyo87
☆

Egypt,
2020-11-22 10:06
(203 d 06:04 ago)

Posting: # 22074
Views: 880

## ambulatory samples in bioequivalence studies [Regulatives / Guidelines]

hi, every one

kindly i need your help to know the accepted deviation in time in ambulatory samples (24, 36, 48 and 72 hr) in bioequivalence studies?? example 6 hours deviation is accepted or not??
Helmut
★★★  Vienna, Austria,
2020-11-23 12:18
(202 d 03:52 ago)

@ yoyo87
Posting: # 22080
Views: 679

## large deviations from schedule

Hi yoyo87,

» […] accepted deviation in time in ambulatory samples (24, 36, 48 and 72 hr) in bioequivalence studies?? example 6 hours deviation is accepted or not?? See also this recent thread. Well, six hours are extreme. I would even collect and analyze a 78 hr sample. Say, it was after the test-treatment and the reference was fine. If you don’t, you end up in your AUC0–tlast comparison with AUC0–48/AUC0–72, which is an apples-and-oranges comparison (negatively biased). If you do, you end up with AUC0–78/AUC0–72, which is positively biased.

Two options (have to be stated in the protocol):
1. Specify a maximum acceptable deviation and – if exceeded – compare AUCs up to the last common time point* (here 48 hrs).
2. If this an IR formulation, specify pAUC0–72 instead of AUC0–tlast as the PK metric for extent of absorption. Work with an imputed (estimated) concentration:
$$C_0=\exp\left(\frac{\log_{e}C_1\cdot(t_2-t_0)+\log_{e}C_2\cdot(t_0-t_1)\;}{t_2-t_1} \right)$$, where the indices $$\small{1,\,2}$$ denote the times and concentrations before and after the estimate denoted by the index $$\small{0}$$.
Say, you have $$\small{t_1=48,\:C_1=16}$$ and $$\small{t_2=78,\:C_2=5.0897}$$.
At $$\small{t_0=72}$$ you will estimate $$\small{C_0\approx\exp\left(\frac{2.77259\times6+1.62722\times24}{30}\right)\approx6.400}$$: See also the second example in this post.
NB, I recommend to always use the linear-up/logarithmic-down trapezoidal rule for the calculation of AUC.

Dif-tor heh smusma 🖖
Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Admin contact
21,518 posts in 4,498 threads, 1,523 registered users;
online 8 (0 registered, 8 guests [including 4 identified bots]).
Forum time: Sunday 17:11 CEST (Europe/Vienna)

A refund for defective software might be nice,
except it would bankrupt the entire software industry
in the first year.    Andrew S. Tanenbaum

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