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The following message was posted to: PharmPK
When working with an IV drug having a direct effect on the AV node of the
heart, I have come across a drug distribution phenomenon where comments from
others with similar experiences would be of value.
The drug is administered in a peripheral vein over a few seconds and in the
initial studies in man samples were drawn in a peripheral vein of the other
arm. As expected the time of intravascular mixing and transit to the other
arm varied and with initial sampling every minute observed Tmax ranged from
1 to 4 minutes post dose (most commonly 2 minutes).
As the site of action is the heart it is of interest to estimate the PK
profile in central circulation even if no arterial samples currently are
available. I assume that a two-step input function might work where the
first is just the input into the central circulation (read: the heart), and
the second the distribution from the heart to the other arm where the
samples were drawn. The question is whether this can be done with the
samples we have available.
A related question is also how to handle the general modeling of a PK
profile when Cmax occurs well after completion of a short term iv injection.
Can the drug input function be approximated by extending the zero order
input up to the observed Tmax, or should a more complex input function be
Looking forward to comments.
Markus Jerling MD PhD
Senior Director of Clinical Research
3172 Porter Drive
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