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I simulated an infusion reponse using Winnolin based on a single IV
bolus data to get the Cmax value. The simulated Cmax value for 30-min
infusion was 200 uM. However, when I calculated the Cmax (the plasma
concentration after 30-min infusion) by the way described below, it
produce a 2 times higher value.
The half-life of this test compound was 0.25 hr. The plasma
concentration achieved after 30-min infusion was about 75% of the
steady state concentration value (Cpss). Cpss was 540 uM calcualted
by the steady state equation. Thus, the plasma concentration value at
30-min infusion was given at 400 uM.
My question is, what causes such a difference condisering the values
should be the same in principle? Thanks in advance for any comments.
P.S. the bolus PK of the test compund was fitting a two-compartment
Hong (Lucy) Lu
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The following message was posted to: PharmPK
Your last statement provides an answer to your question. For a compound
following a bi-exponential decrease in plasma concentrations, one might
see lower initial levels than expected. This is simply due to the fact
that until you have "filled" the second compartment in the model, i.e.
its concentrations are in equilibrium with the central compartment,
plasma concentrations are declining fast. The compound is leaving the
central compartment in 2 directions: to the second compartment and
elimination. Once the infusion is continued for long enough time and the
two compartments are in equilibrium, plasma levels will move toward the
Your question is actually very similar to another one posted last week.
I recommended the other colleague to model the data in hand and simulate
to see what concentrations would be expected and if the simulations
could explain his observations of lower initial levels. Obviously, you
have made the right move from the beginning. This is actually a good
example of the utility of modeling and simulation.
A word of caution is of course that your simulations are based on a
well-established PK model and you are not violating your model
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