Dse and Limitations of the Truncated Area Under the Curve in Bioequivalence Testing

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Abstract
Computer simulations were used to evaluate the truncated area under the plasma level-time curves (AUC.) as indicators of the bioequivalence between test and reference products. Plasma concentrations were simulated from one and two compartment open models using first order absorption rate constants (Ka) and bioavailability (F) ranging respectively from 45 to 200% and 60 to 140% of the reference values. The pharmacokinetic parameters were selected to cover a wide range of disposition rate constants (0.01-0.79 hr.−1). The area under the blood level-time curves was calculated using the trapezoidal rule at each time point (t) according to a conventional sampling regimen. The extent of absorption (AUC.inf) was calculated, using integrals of the general blood equations. The ratios of AUC.: test to reference and AUCL to AUC.were determined. For most simulations, the ratios changed very little between the end of the absorption period, the last time point and the time infinity. AUC, was not a good parameter to compare the bioavailability of two drug products. Three groups of different mathematical behavior were identified, in which bioequivalence determination might present some problems when using a single AUC. Several truncated AUC ratios, however, could provide meaningful information on absorption rates for bioequivalence testing. In our study the AUC80 was consistently a good indicator of bioequivalence.