Truncated AUC evaluates effectively the bioequivalence of drugs with long half-lives

Crossover trials were simulated in order to evaluate whether shortening the duration of bioequivalence trials for drugs with long half-lives would adversely affect the statistical properties of estimated AUC ratios. The trials were simulated under a wide range of assumed kinetic and experimental conditions. The duration of the simulated experiments was gradually shortened and ratios of truncated AUCs were evaluated. In addition, simulations by Martinez and Jackson [1991] were substantially extended. It was demonstrated that the variation of truncated AUCs did not rise, and their bias was negligible when investigations were limited to 2 (and under many conditions to 1) half-lives following drug administration. With large variability of clearance, high limit of quantitation, and/or 2-compartmental models, the observed variation actually often increased when the duration of a study was extended. It was concluded that the assessment of bioequivalence for long half-life drugs would not be adversely affected by limiting the duration of an investigation and, consequently, by using truncated AUCs.