Dear all,
I am developing a PK model for a drug administered as a long-term infusion
of 48 hours using an elastomeric pump. End of infusion was documented, but
sometimes the elastomeric pump was already empty at this time. Therefore
variability of the concentration measurements observed at this time is quite
high.
To address this issue, I try to include variability on infusion duration
assigning the RATE data item in my dataset to -2 and model duration in the
PK routine. Since the "true" infusion duration can only be shorter than the
documented one, implementing IIV with a log-normal distribution
(D1=DUR*EXP(ETA(1)) cannot describe the situation.
I tried the following expression, where DUR ist the documented infusion
duration:
D1=DUR-THETA(1)*EXP(ETA(1))
It works but does not really describe the situation either, since I expect
the deviations from my infusion duration to be left skewed. I was wondering
if there are any other possibilities to incorporate variability in a more
suitable way? All suggestions will be highly appreciated!
Thank you very much in advance!
Patricia
