joyjac
★    

Philippines,
2006-06-28 08:56
(6600 d 06:56 ago)

Posting: # 157
Views: 7,561
 

 Restrictions on Subjects Movement during BE [Design Issues]

Hi! I would like to get your thoughts on this. During the BE study, while lying in bed or in supine position is Not allowed after drug intake for at least 2 hours, can the volunteer subjects be allowed to stay standing, sitting or walking i.e. limited activity around the room where they stay after dose?

I understand that posture and physical activity of the subjects must be standardized, meals and fluid intake as well, during the study as the bioavailability of an active moiety from a dosage form could be dependent upon GI transit times, posture and physical activity.

I appreciate inputs on the above. Thanks.
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2006-07-05 16:54
(6592 d 22:59 ago)

@ joyjac
Posting: # 158
Views: 5,967
 

 Restrictions on Subjects Movement during BE

Hello Joy!

Just a few desultory thoughts...

❝ During the BE study, while lying in bed or in supine position is Not allowed after drug intake for at least 2 hours, can the volunteer subjects be allowed to stay standing, sitting or walking i.e. limited activity around the room where they stay after dose?


I remember one of Paula Muñiz Piniella’s lectures (hopefully correctly):
Two studies on a modified release formulation (gastric resistant); both demonstrated bioequivalence in the fed state, but:
  • Study 1: CV was 20% for AUC, and 25% for Cmax, and
  • Study 2: CV was about 11% for both metrics.
Why?
Since designs of both studies were essentially the same, let's look at the difference:
in the first study—in a large CRO—the administration was in standing position followed by 20 minutes sitting, then 1 hour lying on the right side, then 3 hours lying, whereas
in the second study—in a small CRO—administration was in standing position followed by sitting until 4 hours post dose.
One can only speculate that the over-restriction in the first study introduced variability: although under close observation, at least subjects may have moved only in one study period (lying on the right side for 1 hours is very uncomfortably) thus increasing the CV…
Moral of the story: the bigger is not always the better ;-)

❝ I understand that posture and physical activity of the subjects must be standardized, meals and fluid intake as well, during the study as the bioavailability of an active moiety from a dosage form could be dependent upon GI transit times, posture and physical activity.


Full ACK, but over-standardisation may lead to an ‘own goal’ (see above).
Of course sporting activities should be avoided (no ping-pong and tabletop football in the ward), but also exciting movies (whatever that means, maybe ‘Rambo I-III’ for males, and ‘Love Story’ for females)…
In my experience the atmosphere in mixed-sex studies is much more less tense than in ‘males-only’ ones ;-)

Don’t forget to standardise nutrition (subjects don’t like it, but it is a necessity to serve the same meals in all treatment periods); it may be an option to individualise the amount of meals for males/females.
Another point is food interaction, e.g., broccoli and grilled meat induces CYP1A2, whereas grapefruit juice inhibits CYP3A4; meals with a high content of proteins may increase liver blood flow, thus decreasing hepatic extraction of IR high clearance drugs…
Since up to 50% of the population show headaches upon caffeine withdrawal, you also may consider allowing some coffee—let’s say 4 hours post dose, if your drug is not metabolized by CYP1A2…

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
UA Flag
Activity
 Admin contact
23,117 posts in 4,859 threads, 1,647 registered users;
40 visitors (0 registered, 40 guests [including 7 identified bots]).
Forum time: 15:53 CEST (Europe/Vienna)

You can’t really say “similar” if it’s the same again you want.
“Similar” means something different.    Anthony Burgess

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