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Dear Colleagues,
In most cases we calculate MRT but I have a feeling
that we are not using this parameter to its full
capacity. I hope that following generate some
interesting conversation within the group. Under the
situation that we have not achieved
pseudo-equilibrium, a typical concept of elimination
half-life dose not quite hold, as the plasma
elimination half-life is not reflective of drug
elimination from the body (50% decline in the plasma
does not correspond with 50% decline in the
tissues/body). What about MRT? Under non-equilibrium
conditions, dose the MRT (calculated from plasma data)
represents the time for 63% of the administrated dose
to be eliminated from plasma compartment of the whole
body? How accurate or appropriate is the calculation
and use of MRT for multi-compartment model (i.e.,
two-compartment model)?
Riegelman and Collier published an excellent paper
(Journal of Pharmacokinetics and Biopharmaceutics, vol
8, No. 5, 1980) on this topic, which I have consulted
but would appreciate any further comments or input.
Thanks
Rostam
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Rostam,
It is my understanding that MRT calculated using non-compartmental
methods has no meaning for predicting anything at any specific time
after the dose. It is a time-independent parameter describing the
average residence time of a molecule observed from 0 to infinite time.
If you want to predict amounts in the body at specific times then you
must resort to methods e.g. compartmental models, that can meaningfully
include time as the independent variable.
Nick
Nick Holford, Divn Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-at-.auckland.ac.nz
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)