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Considering a drug that follows a 2-compartment open body model, does
anyone have physiological examples of where K21 is altered but K12
remains relatively constant? I am assuming that changes in most
efflux transporters would alter both K12 and K21. I thought about ion
trapping within tissues, but am not aware of any physiological state
would result in a generalized change in tissue pH without also
altering blood flow.
Marilyn
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Marilyn,
> Considering a drug that follows a 2-compartment open body model, does
> anyone have physiological examples of where K21 is altered but K12
> remains relatively constant?
It may help if you change from an algebraic view of PK to a
physiological view of PK. There is no physiological entity that
corresponds to K12 and K21. In the same way there is no physiological
entity that corresponds to K for a one compartment model. These
'constants' are dependant on the ratio of parameters (clearances and
volumes) that are more closely linked to physiology and anatomy.
If you think of a 2 compartment model in terms of elimination clearance
(CL), distribution clearance (Q), central volume (V1) and tissue volume
(V2) then:
K21=Q/V2 and K12=CL/V1
So in answer to your question -- you can change either Q (blood flow) or
V2 (tissue volume and partition coefficient) and this will change K21
without changing K12 if there is no change in central compartment volume
and no change in elimination clearance.
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.aaa.auckland.ac.nz
www.health.auckland.ac.nz/pharmacology/staff/nholford
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The following message was posted to: PharmPK
Hi,
I wasn't thinking too clearly when I wrote this reply. Please note
this correction:
If you think of a 2 compartment model in terms of elimination clearance
(CL), distribution clearance (Q), central volume (V1) and tissue volume
(V2) then:
K21=Q/V2 and K12=Q/V1
So in answer to your question -- you can change V2 (tissue volume and
partition coefficient) and this will change K21
without changing K12 if there is no change in central compartment
volume and no change in distribution clearance.
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.-at-.auckland.ac.nz
www.health.auckland.ac.nz/pharmacology/staff/nholford
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