Wolfsegger, Martin J. and Jaki, Thomas (2005) Estimation of AUC from 0 to Infinity in Serial Sacrifice Designs. Journal of Pharmacokinetics and Pharmacodynamics, 32 (5-6). pp. 757-766.
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.
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