A Note on the Calculation of Intrasubject Coeffi cient of Variation in Bioequivalence Trails

The most common pharmacokinetic responses of the rate and the extent of absorption are: Area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), and time to reach maximum plasma concentration (tmax). The distributions of responses such as AUC and Cmax are often positively skewed and exhibit a lack of homogeneity of variances. Therefore, normality assumption on AUC and Cmax may not be suitable. In this case, the assessment of average BE based on raw data and normality assumptions may not be appropriate. Logarithmic transformation is the commonly chosen data transformation technique for BE studies and is also recommended by the FDA “Guidance on Statistical Procedures for Bioequivalence Studies using a Standard Two-Treatment Crossover Design (July 1992)”.