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I would want to know which is the most appropiate curve to use when
determining the pharmacokinetic parameters of single compartment
model drugs oral drug administration. Because I have found out that
the following two curves their shapes is the same.
1 A graph of concentration versus time
2 A graph of log of concentration versus time (semilogarithm curve)
Which of the two is most accurate?
Ogwal Sidney
Lecturer Department of Pharmacy
MaKerere University Kampala
Uganda
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[Two replies  you might also look at
http://www.boomer.org/c/p1/Ch04/Ch0403.html and pages following  db]
From: Jeffrey Larson
Date: Thu, 23 May 2002 15:31:56 0500
To: david.at.boomer.org
Subject: RE: PharmPK Pharmacokinetic parameters oral drug Administration
Dr. Sidney
The curves should be different and indicate whether the elimination process
is zero order or first order. Zero order elimination will graph as a
straight line on a concentration versus time scale, while first order will
graph as a straight line on a log concentration versus time scale.
Most drugs will follow a first order elimination where the amount of drug
eliminated over time is dependent on the concentration of drug in the body.
However, you might be seeing zero order kinetics if the rate of absorption
is greater than the rate of elimination (flip flop kinetics).
I hope this helps answer your question.
Jeffrey L. Larson, Ph.D.
Director of Toxicology and Pharmacokinetics
Tanox, Inc.
4888 Loop Central Drive
Houston, TX 770812225
(713) 5784212

From: Nick Holford
Date: Fri, 24 May 2002 08:33:07 +1200
To: david.aaa.boomer.org
Subject: Re: PharmPK Pharmacokinetic parameters oral drug Administration
>
> I would want to know which is the most appropiate curve to use when
> determining the pharmacokinetic parameters of single compartment
> model drugs oral drug administration. Because I have found out that
> the following two curves their shapes is the same.
>
> 1 A graph of concentration versus time
> 2 A graph of log of concentration versus time (semilogarithm curve)
>
> Which of the two is most accurate?
If a graph of conc vs time and log conc vs time have the same shape
then I wonder if you have made a mistake in your graph.
The parameters I would be interested in would be clearance, volume of
distribution to describe elimination and distribution, and perhaps
absorption halflife and lagtime to describe input. Rough estimates
of these parameters can be obtained by graphical means but a more
serious effort would involve some other method e.g. nonlinear
regression using a program such as WinNonLin.
Nick

Nick Holford, Divn Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:n.holford.a.auckland.ac.nz
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm
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Ogwal,
You wrote:
> I would want to know which is the most appropiate curve to use when
> determining the pharmacokinetic parameters of single compartment model
> drugs oral drug administration. Because I have found out that the
> following two curves their shapes is the same...
Our free demo of PK Solutions illustrates sidebyside the normal and
semilog plots plasma level data following oral dosing. See
http://www.SummitPK.com/
I don't think it is a question of which plot is the "more accurate." I
for one would be curious to see your concentration  time data set to in
fact verify that the curves are the same.
One distinction I might offer is that the normal plot is used for
graphical analysis (such as with the trapezoid rule) to obtain AUC and
related "modelindependent" pk parameters. Whereas, the semilog
transformation is the starting point for obtaining exponential terms,
the sum of which describe the curve mathematically and the their
coefficients are used to calculate a vast variety of pk parameters,
including the AUC set. Thus, each curve is the starting point for a
different mathematical approach for calculating pharmacokinetic
parameters.
A listing of pharmacokinetic equations appropriate to both mathematical
methods is also available from the above mentioned web site.
Best Regards,
David
David S. Farrier, Ph.D.
Summit Research Services
68911 Open Field Dr. Email: DFarrier.aaa.SummitPK.com
Montrose, CO 81401 Web: http://www.SummitPK.com
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Dear Sidney,
usually we use both curves to show the behaviour of the drug. The linear
plot permit us to have a view of Cmax and Tmax parameter as well as their
variability between subjects. On the other hand with the semilogarithm plot
we can estimate parameters as t1/2 (elimination halflife),apparent
elimination rate constant,....
Therefore I consider that you should use linear and semilogarithm curves in
your determinations because both give you important information about your
drug.
I hope it helps.
Best regards
Daniel Martínez
RIA Laboratory
Metabolism & Pharmacokinetics Service
Research & Development Department
IPSEN PHARMA, S.A.
Ctra. Laureŕ Miró 395
Sant Feliu de Llobregat, Barcelona, Spain
daniel.martinez.aaa.beaufouripsen.com
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Copyright 19952010 David W. A. Bourne (david@boomer.org)