BIOEQUIVALENCE - PERFORMANCE OF SEVERAL MEASURES OF EXTENT OF ABSORPTION

The determination of the area under the concentration-time curve (AUC) is the method most commonly used by regulatory agencies to assess ext ent of drug absorption after single-dose administration of oral produc ts. Using simulations, several approaches toward measuring the actual area, in whole or part, were tested. In addition, the performance of t he peak concentration (C-max), usually taken as a measure of the rate of absorption was assessed evaluating extent. Model scenarios for drug s with typical mean characteristics and statistical distributions were investigated. Using different kinetic models of disposition, the time course of the drug concentration in plasma was simulated. Intraindivi dual and interindividual variability and assay error were modeled usin g Monte Carlo techniques. The accuracy, precision, and ease of use of the various measures of extent were evaluated, and statistical power a nalyses were performed. Among the measures tested, the most reliable w ere the AUC computed up to the time of the last quantifiable concentra tion, without extrapolation, and C-max. However, being also sensitive to rate, C-max as a measure of extent is of limited potential.