Abstract
Nonclinical in vivo animal studies have to be completed before starting clinical studies of the pharmacokinetic behavior of a drug in humans. The drug exposure in animal studies is often measured by the area under the concentration time curve (AUC). The classical complete data design where each animal is sampled for analysis once per time point is usually only applicable for large animals. In the case of rats and mice, where blood sampling is restricted, the batch design or the serial sacrifice design need to be considered. 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. This paper presents an estimator for AUC from 0 to infinity in serial sacrifice designs, the corresponding variance and its asymptotic distribution.
Similar content being viewed by others
References
A.J. Bailer (1988) ArticleTitleTesting for the equality of area under the curves when using destructive measurement techniques J Pharmacokinet. Biop. 16 IssueID3 303–309 Occurrence Handle1:STN:280:BiaC38rjs1A%3D
J.R. Nedelman E. Gibiansky D.T.W. Lau (1995) ArticleTitleApplying Bailer’s method for AUC confidence intervals to sparse sampling Pharmaceut Res. 12 IssueID1 124–128 Occurrence Handle10.1023/A:1016255124336 Occurrence Handle1:CAS:528:DyaK2MXjt12it7k%3D
J. Singer M. Berger (2003) ArticleTitleThe Jackknife applied to incomplete blood sampling models Pharmaceut. Stat. 2 IssueID3 161–166
D.J. Holder F. Hsuan R. Dixit K. Soper (1999) ArticleTitleA method for estimating and testing area under the curve in serial sacrifice, batch, and complete data designs J. Biopharm. Stat. 9 IssueID3 451–464 Occurrence Handle10.1081/BIP-100101187 Occurrence Handle10473031 Occurrence Handle1:STN:280:DyaK1MvgtVSisg%3D%3D
J. Yuan (1993) ArticleTitleEstimation of variance for AUC in animal studies Journal of Pharmaceut. Sci. 82 IssueID7 761–763 Occurrence Handle1:CAS:528:DyaK3sXltlSru7s%3D
M. Gibaldi D. Perrier (1982) Pharmacokinetics EditionNumber2 Marcel Dekker New York 411
B. Efron R.J. Tibshirani (1993) An Introduction to the Bootstrap Chapman and Hall London 326
J. Shao D. Tu (1996) The Jackknife and Bootstrap Springer New York 168
Davison A.C., Hinkley DV. Bootstrap Methods and their Applications. Cambridge Series in Statistical and Probabilistic Mathematics. Cambridge University Press, 1999, p. 212
A.W. Vander Vaart (1998) Asymptotic Statistics Cambridge University Press United Kingdom 26
R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria (2004)
M. Ploner. Bootstrap confidence intervals – an overview and comparisons by means of selected applications. Ph.D dissertation, University of Vienna (2002)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wolfsegger, M.J., Jaki, T. Estimation of AUC from 0 to Infinity in Serial Sacrifice Designs. J Pharmacokinet Pharmacodyn 32, 757–766 (2005). https://doi.org/10.1007/s10928-005-0044-0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10928-005-0044-0