All Times EDT
Keywords: Partial AUC, Destructive Sampling Design
Product blood level in vivo bioequivalence (BE) studies typically involve complete blood concentration-time profiles generated for each subject. Each subject then provides the estimates of the rate and extent of drug absorption. However, repeated blood draws are not always feasible for studies using small animals because of handling or blood volume (e.g. fish). Several proposals have been published for comparing the product extent of absorption when complete profiles from each study subject are not available; however, the issue of comparing the rate of absorption remains unresolved. Our research focuses on the absorption rate comparison in BE studies using a destructive sampling design (one blood sample per subject). We propose to apply the Bailer-Satterthwaite confidence interval for estimating the ratio of partial areas. To characterize the behavior of this approach, we examine the impact of partial area cutoff time, blood sampling schedule, and the number of subjects included at each sampling time. Using simulated situations reflective of the those with issues encountered with immediate release veterinary formulations, we compare BE conclusions resulting from the use of this approach to simulated results that assuming repeated blood draws from each study subject.