Duquesnoy C, Lacey L F, Keene O N, Bye A
Department of Clinical Pharmacology, Laboratoire Glaxo Wellcome, 20, rue Rouget de Lisle, 92 442 Issy les Moulineaux Cedex, France.
Eur J Pharm Sci. 1998 Oct;6(4):259-64. doi: 10.1016/s0928-0987(97)10023-9.
The performance of different partial AUCs, including partial AUC from zero to t(max) of the reference formulation (AUC(r)) and partial AUC from zero to tmax of test or reference formulation, whichever occurs earliest (AUC(e), as indirect measures of rate of absorption have been evaluated using simulated experiments. The performance of these metrics relative to C(max), t(max) and C(max)/AUC(infinity) was further assessed using the results of actual studies involving a Glaxo drug. The normalised metrics AUC(r)/AUC(infinity) and AUC(e)/AUC(infinity) have also been evaluated. Our provisional conclusions were: (1) AUC(r)/AUC(infinity) and AUC(e)/AUC(infinity) had greater statistical power than C(max) and the non-normalised partial AUCs at detecting true differences in rate of absorption. Using real data, the performance of AUC(e)/AUC(infinity) was poor, however, the performance of AUC(r)/AUC(infinity) was good; (2) C(max)/AUC(infinity) was more precisely estimated than AUC(r)/AUC(infinity) or AUC(e)/AUC(infinity) and may be a superior metric for assessing absorption rates of highly variable drugs.
已使用模拟实验评估了不同部分AUC的性能，包括参比制剂从零到t(max)的部分AUC（AUC(r)）以及测试制剂或参比制剂从零到最早出现的tmax的部分AUC（AUC(e)），作为吸收速率的间接测量指标。使用涉及葛兰素史克公司一种药物的实际研究结果，进一步评估了这些指标相对于C(max)、t(max)和C(max)/AUC(∞)的性能。还评估了标准化指标AUC(r)/AUC(∞)和AUC(e)/AUC(∞)。我们的初步结论是：(1) 在检测吸收速率的真实差异方面，AUC(r)/AUC(∞)和AUC(e)/AUC(∞)比C(max)和未标准化的部分AUC具有更大的统计功效。使用实际数据时，AUC(e)/AUC(∞)的性能较差，然而，AUC(r)/AUC(∞)的性能良好；(2) C(max)/AUC(∞)比AUC(r)/AUC(∞)或AUC(e)/AUC(∞)估计得更精确，可能是评估高变异药物吸收速率的更优指标。
