The Degrees of Correlation in Bioavailability Parameters and the Confidence Regions in Bioequivalence Study

HSING-CHU HSU AND *HAI-LIN LU

Department of Pharmaceutics, Chia Nan Jr. College of Pharmacy,
*Computer Center, Chia Nan Jr. College of Pharmacy, 72-1, Pau-an, Jen-teh hsiang, Tainan hsien, Taiwan, R.O.C.

ABSTRACT

   The parameters to define the shape of the 1-α confidence ellipse constructed by the Cmax and AUC infinite, the physical meanings of the shape of the ellipse, correlation of the Cmax and AUC infinite, and confidence regions of two 95% confidence intervals and the 90% confidence ellipse was described and discussed. The ratio of the lengths of the major and minor axes for the confidence ellipse was a proportional function of the coefficient of correlation between the two relevant bioavailability variables, The degree of correlation could vary significantly from one bioequivalence study to another. The degree of correlation has great impact on the probability of confidence region and, hence, in univariate analysis each bioequivalence decision-making would be unavoidably based on the different probability, Examples of the bioequivalence study of nine drugs were demonstrated. In order to assess bioequivalence with a consistent probability, the bivariate method using two 90% confidence ellipses of reference and test products is proposed. Since each available statistical method has its limitation and shortocoming, it is desirable to evaluate bioequivalence using multiple assessment methods.

Key words : Correlation, Cmax, AUC infinite, Confidence ellipse, Confidence region