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The following message was posted to: PharmPK
Dear all,
Does anyone have information about the appropriate probability
distribution of
lag time of absorption (Tlag) for Monte Carlo simulations? Since Tlag
obtained
from biostudies is a discrete ordinal variable, I have difficulties
including
its variability in the simulation. Thank you.
Best Regards,
Prapoch Watanalumlerd (Keng)
Pharmaceutic graduate student
College of Pharmacy, Oregon State University
Phone: 541-737-5789
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The following message was posted to: PharmPK
Dear Keng,
You wrote:
> Does anyone have information about the appropriate probability
> distribution of lag time of absorption (Tlag) for Monte Carlo
> simulations?
> Since Tlag obtained from biostudies is a discrete ordinal variable,
> I have difficulties including its variability in the simulation.
For most, if not all, a log-normal distribution of PK parameters is the
logical choice (as was discussed recently in this group). I do no see a
specific reason why this would not hold for the lag time of absorption
(Tlag). IMHO, this is the logical choice in case you are using a PK
model
including a lag time. If you estimate Tlag from a series of
measurements,
the obtained value is not a discrete variable, but an estimate of the
'true'
Tlag.
Possibly you are referring to a noncompartmental approach where Tlag is
defined as the last measured time point where the concentration is zero
(or
more precisely, below the LOD, or LOQ, or whatever criterion is
defined). In
this case Tlag is indeed a discrete ordinal variable. Since the 'true'
Tlag
may still be described by a log-normal distribution, the following
approach
could be used. Given a geometric mean and standard deviation for Tlag,
the
probability that Tlag is between 0 and t1 (time of first measurement)
can be
calculated, and this is the probability that the observed Tlag is 0,
i.e.
the probability that at t1 at least some drug has been absorbed.
Similarly,
the probability that Tlag is between t1 and t2 (time of first
measurement)
equals the probability that the observed Tlag is t1 (i.e. at least some
drug
absorbed at t2), et cetera.
Any suggestions about this approach are welcomed.
Best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.-at-.farm.rug.nl
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)