Minimum running time Subject

This type of hADME study will always have an explorative character, and typically comprises less than the normal minimum of 12 subjects for a PK study. If the compound is expected to show different and unpredictable ADME characteristics in special populations, then it might be necessary to include these populations in addition to normal, healthy subjects. Or, if other conditions might influence ADME in an unpredictable manner (e.g. food effects), then it might even be necessary to run the study in a cross-over design. The inclusion of females (being not of childbearing potential) was discussed several times, but it seems to be a rare exception for hADME studies. 

The quality of the approximation of the inter-repair time distribution is goo4 but deteriorates once the number of source processes decreases. This is especially the case when the interarrival time of the source processes is non-exponential. Using Taylor expansions, Blumenthal et al. (1973) derived correction factors for the exponential interarrival time if the number of source processes n is small or t is finite. A finite time t introduces an error due to the fact that the process has not been running very long, which means that the asymptotic results may not be valid. Whether or not these correction factors can be used as an indication of the minimum number of source processes is the subject of further research. 

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