joyjac ★ Philippines, 2006-06-28 08:56 (6305 d 10:09 ago) Posting: # 157 Views: 6,826 |
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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 ★★★ ![]() ![]() Vienna, Austria, 2006-07-05 16:54 (6298 d 02:12 ago) @ joyjac Posting: # 158 Views: 5,438 |
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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:
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! ![]() Helmut Schütz ![]() The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |