Journal of Pharmacokinetics and Pharmacodynamics

, Volume 34, Issue 1, pp 103–113

Establishing Bioequivalence in Serial Sacrifice Designs

Article

DOI: 10.1007/s10928-006-9037-x

Cite this article as:
Wolfsegger, M.J. J Pharmacokinet Pharmacodyn (2007) 34: 103. doi:10.1007/s10928-006-9037-x

Nonclinical in vivo animal studies have to be completed before starting clinical studies of the pharmacokinetic behavior of a drug in human subjects. The classic complete data design, where each animal is sampled for analysis once per time point, is usually only applicable for large animals using the traditional two-stage approach. The first stage involves estimation of pharmacokinetic parameters for each animal separately and the second stage uses the individual parameter estimates for statistical inference. In the case of rats and mice, where blood sampling is restricted, the batch design or the serial sacrifice design may be applicable. In batch designs samples are taken more than once from each animal, but not at all time points. In serial sacrifice designs only one sample is taken from each animal. In this paper, three methods are presented to construct confidence intervals for the ratio of two AUCs assessed in a serial sacrifice design, which can be used to assess bioequivalence in this parameter. The presented methods are compared in a simulation study.

Keywords

AUCbioequivalencebootstrapFieller’s theoremSatterthwaite’s approximationserial sacrifice designsparse sampling

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.Department of BiostatisticsBaxter AGViennaAustria