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The following message was posted to: PharmPK
Dear All
I have a problem with some regulatory bodies when selecting the
number of concentrationtime points during the elimination phase in
bioequivalence studies. Usually I try my best to use more than 3
points ( which is prefered statistically) but some times I have to
stick to three points due to the fact that in some volunteers if I
use 4 or more points I will include the distribution phase. My
question is:
Is using three points not acceptible. I will appreciate all
contributions especially from regulators.
Mutasim Al-Ghazawi, Ph.D
Faculty of Pharmacy, University of Jordan
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[Two replies - db]
From: Manish Issar
Date: Tue, 10 Jul 2001 13:25:23 -0400
To: david.aaa.boomer.org
Subject: Re: PharmPK Number of points for Ke
hi
regarding the selection of time points for estimation of terminal half
life it is advisable to use at least 4-5 points in order to get a
reasonably close estimate of terminal half life. As u have said that in
your study u cannot use 4 because then u might end up using the points
from the distribution phase. in this case then it is advisable that u
must improve the sensitivity of ur assay and then try to determine the
terminal half life. it seems that the drug is still in the distributive
phase. i am sure by doing this u will encounter a totally different
estimate for terminal half life. with ur curent use of 3 points u are
trying to underestimate the desired pharmacokinetic parameter. If
feasible try using LC/MS/MS to analyse ur samples.
hope this helps.
manish
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From: DrLuckow.and.Associates.-at-.t-online.de (320027289205)
Date: Tue, 10 Jul 2001 21:53:23 +0200
To: david.-at-.boomer.org
Subject: Re: PharmPK Number of points for Ke
The following message was posted to: PharmPK
Dear all,
to answer that question I carried out a lot of simulations with a
Bateman function using 8 time points in the terminal phase which was
weighted with a random scatter ranging from +- 10 % to +- 140 % on each
individual data point. Terminal half-lives were calculated by
semi-logarithmic regression of the last 4, 6, and 8 data ponts,
respectively. A result was regarded as rational when the coefficient of
correation was significantly larger than zero (p = 0.05, one-sided
test).
As a result, 8 and 6 (most probably although not tested: even 5) data
points will always give a significant result. Four data points will
result in a significant semilogarithmic regression only if the scatter
of data points is smaller than 40 %.
In the case of 3 points only you should by all means demonstrate by
testing r for significance that the result is rational.
I am crossing my fingers that such a reasoning will convince the
regulatory officials.
Regards
Volker
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