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Dear group,
The MRT is defined conceptually for an iv bolus.
It is calculated as AUMC/AUC.
Is it acceptable to use the same formula for an oral administration ?
If yes, can one say that the "MRT" obtained by this formula will not
correspond for an oral formulation to the definition of the MRT for an
iv bolus, but to the MRT for an iv bolus + the mean absorption time ?
I would like above all to know if in the practice it is usual to
calculate the "MRT" for an oral formulation in this way, providing that
one has clear in his mind what the result means.
Can this also be applied to the calculation of the "MRT" of slow or
extended release oral formulations ?
Many thanks in advance
Margherita Strolin Benedetti & Pascal Espié
UCB Pharma
Belgium
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Hello,
As you wrote, MRT is conceptually defined for an instataneous input.
After
a po administration, the relationship AUMC/AUC equals MRT plus a Mean
"Absorption" Time (MAT). This MAT includes (mean) disolution time and
other processes that may occur before the drug reaches the blood stream.
After an extravascular administration, drug´s residence time in the
body
changes, but not the MRT as a concept (AUMC/AUC after instantaneous
input).
In a linear system, MRT should be constant in the whole range of doses.
So, as some authors stated, the use of the notation MRTx (where x = po,
im,
sc...... or any other route of administration) may be lead to confusion.
Hope this helps
José Antonio Allué
Mass Spectrometry Laboratory
Metabolism & Pharmacokinetics Service
Research & Development Department
IPSEN-PHARMA S.A. Laboratories
Ctra. Laureà Miró 395
Sant Feliu de Llobregat, Barcelona, Spain
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Dear Margherita Strolin Benedetti & Pascal Espié:
May I suggest the following reference:
Karol, Michael D., Mean Residence Time and the Meaning of AUMC/AUC,
Biopharmaceutics & Drug Disposition, Vol. 11, 179-181 (1990)
Michael
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)