Mauger D T, Chinchilli V M
The Pennsylvania State University, Department of Health Evaluation Sciences, H173, 500 University Drive, Hershey, PA 17033, USA.
Stat Med. 2000 Oct 30;19(20):2855-66. doi: 10.1002/1097-0258(20001030)19:20<2855::aid-sim550>3.0.co;2-t.
In a typical bioequivalence trial, summary measures of the plasma concentration versus time profile are used to compare two formulations of a drug product. Commonly used measures include area under the curve (AUC), maximum plasma concentration (C(max)) and time to maximum concentration (T(max)). Equivalence of these summary measures, in general, does not guarantee equivalence of the entire profile. Rescigno and Chinchilli and Elswick propose indices which measure profile similarity, but can be overly sensitive to unimportant differences and are not easily interpreted pharmacologically. We propose an alternative index based on smoothing the relative difference between bioavailability profiles. This provides a method for assessing bioequivalence over the entire profile which has a familiar interpretation and can be tuned to provide a compromise between the insensitivity to pattern differences of summary measures and the oversensitivity of pointwise comparisons.
在典型的生物等效性试验中，血浆浓度随时间变化曲线的汇总指标用于比较药品的两种剂型。常用指标包括曲线下面积（AUC）、最大血浆浓度（C(max)）和达峰时间（T(max)）。一般来说，这些汇总指标的等效性并不能保证整个曲线的等效性。Rescigno、Chinchilli和Elswick提出了测量曲线相似性的指标，但这些指标可能对不重要的差异过于敏感，且在药理学上不易解释。我们提出了一种基于生物利用度曲线相对差异平滑处理的替代指标。这提供了一种评估整个曲线生物等效性的方法，该方法具有常见的解释，并且可以进行调整，以在汇总指标对模式差异的不敏感性和逐点比较的过度敏感性之间达成折衷。
