Back to the Top
Dear all,
I am trying to determine the half life of a compound in rats following
a single iv bolus. 4 rats were dosed 1 mpk by tail vein and plasma
samples were collected at predose, 0.5, 1,2,4,8 h. By just looking at
the plasma concentrations, it appears that most of it is eliminated
within the first half hour. The plasma level drops off very steeply
over the next few hours and are slightly above the lloq. In two
animals they almost plateau out between the 2-8 hour intervals. I get
very variable elimination t1/2s in the four animals depending upon what
time points I include-t1/2 varies from 30 min to 4 hours.
My question is that following a single iv bolus dose for a drug with
very short half life (say 10 min), does it make sense to calculate any
pk parameters from time points collected post 3-4 t1/2s (2-8 hours in
the above case). Thanks.
-Saileta
Back to the Top
The following message was posted to: PharmPK
Dear Saileta
If levels are detectabale with confidence then they must be
included.
I feel in your case they need to be dropped. This is because you
are getting levels very close to LLOQ. If change in concentration
in the two subsequent reading is very minimal then the validity of
such data becomes questionable.
Personally I would accept two subsequent data of Last samples (for
a drug with very long half life or very short half life as in this
case) and if values lie very close to LLOQ whenever the difference
between the values is about LLOQ. This I call discriminative power
of the method.
For a method with LLOQ 10 ng / ml, it is interesting to know how
results of two samples with concentration 12 and 15 ng/ ml would
be obtained.
All said, it is necessary to apply some pharmacodynamic/ clinical
logic whether such data (as obtained by you) is worth analysing
pharmacokinetically. In any case all the omissions must be
documented.
with best regards
Dr. Prashant
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)