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In the studies of the pharmacokinetics of a drug, I have found that it
is very rapidly eliminated in the first 2 hours (more rapidly in the
IV-bolus compared to oral) and then the levels stay very low for the
next two hours at which point I had no more collected any data, but
these levels are just slightly above the detection limit. Modelling the
data using noncompartmental modelling would give very different
half-lives, depending on where I drew the lambda-Z region; a half-life
of 30 minute vs a half-life of 400 minutes depending on how the line was
drawn. I tried fitting the data into compartmental models and
2-compartmental models seem to nicely fit the oral data, while the iv
data could be fitted by both one or two compartment model. The beta
half-life obtained by the two-compartmental modelling of oral data for
instance, also leans more towards the longer, ie. 500 minute half-life.
The ratio of K12 to k21 being more or equal 4, probably indicative of a
distribution phase. Can anyone help me with the best way to determine
the proper half-life here?
At least visually speaking, hardly anything is left two hours post
dosing, which could reflect a short half-life and yet some small amounts
tend to persist and form a plateau for some time after that. so, I guess
it is a classical case of a very steep elimination at first, followed by
an almost flat residual elimination.
Any comments would be greatly appreciated.
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