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Within my company we are currently discussing whether or not to report
the parameters MRT (mean residence time) and Vss (volume of distribution
at steady state) as part of the non-compartmental PK analysis of phase I
human volunteer studies. One element in this discussion are the
difficulties regarding the calculation (extrapolation error) and the
interpretation of these parameters. However, it is also relevant to us
to what extent regulatory authorities are used to getting these
parameters and dealing with them. Therefore I would like to initiate
this small survey.
Colleagues in the pharma-industry and hopefully from regulatory
authorities are kindly asked to reflect upon the following questions
Are these parameters usually reported in human PK studies, wherever
Furthermore, more specific, is reporting of these parameters dependent
on the route of administration, e.g. only for IV administration, or not?
Regarding nomenclature: Do you specify the route of administration, e.g.
in a suffix MRToral, MRTsc, MRTiv, MRTiv,inf, etc?
MRT is calculated as AUMCinfinity/AUCinfinity. Do you use a maximally
acceptable percentage for the extrapolated part of the AUMCinfinity.
Similar to the 20 % extrapolation that is often used for AUCinfity?
Thanks in advance to anyone willing to respond to this survey.
Dept. of Clinical Pharmacology & Kinetics,
ORGANON, Oss, the Netherlands.
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Regarding your question about nomenclature, I think you should specify
the route of administration e.g. after oral administration the MRT is
indicative of both absorption and systemic disposition i.e. MRT is
Mean Absorption Time (MAT) + Systemic Mean Residence Time (MRTsys)
whereas for IV bolus administration MRT reflects only systemic
disposition and is thus the same as systemic mean residence time
Department of Pharmaceutics
Virginia Commonwealth University
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