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3Â¥2013-05-03 16:28:08
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4Â¥2013-05-04 22:13:53
zhoupeng87
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5Â¥2013-05-06 10:06:25
zhangxuan200
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Endrenyi and co-workers (1991, 1993) were the first to show that Cmax/AUC is a better characteristic of the absorption rate than Cmax itself. They showed that the ratio Cmax/AUC is independent of both within-subject variations and possible differences in the extent of absorption and ¨C in the case of a one-compartment body model with firstorder absorption ¨C reflects only the contrast between the absorption and disposition rate constants, ka/kel. Lacey et al. (1994) considered simulated and real experiments and came up with the conclusion that Cmax/AUC is a more powerful metric than Cmax in establishing bioequivalence when formulations are truly bioequivalent, and that Cmax/AUC is more sensitive than Cmax at detecting differences in rate of absorption when they exist. Schall and co-workers (1994) showed that under fairly general conditions tmax and Cmax/AUC are equivalent characteristics of the absorption rate. Cmax/AUC can be observed with higher precision, and is easier to handle statistically than tmax. On the basis of data from 20 bioequivalence studies they came up with the rather subtle recommendation that for drugs with short (<5 hours) elimination half-lives or fastest disposition half-lives in the case of higher compartmental models, Cmax/AUC is the best rate characteristic, but that for drugs with long elimination or fastest disposition half-lives, tmax can be superior to Cmax/AUC. |
6Â¥2013-05-14 08:48:19
7Â¥2014-05-25 18:18:23














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