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PharmPK - Discussions about Pharmacokinetics
Pharmacodynamics and related topics
Dear readers,
Would anyone teach me which parameter, mean or median, is usually used in
evaluating the typical plasma profile and PK population parameters for the
data has the large inter-individual variability.
Thanks in advance.
Yasuo Koyama
koyamay.at.anet.ne.jp
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[db - another multireply question ;-)]
From: "Bonate, Peter, HMR/US"
To: "'PharmPK.aaa.pharm.cpb.uokhsc.edu'"
Subject: RE: Median and Mean
Date: Mon, 20 Oct 1997 16:06:57 -0500
X-Priority: 3
Mime-Version: 1.0
Whether to choose the median or mean depends on the distribution of the
data. Typically, pk parameters are log-normally distributed, in which
case the most appropriate parameter is the median. Unfortunately, most
scientists mis-represent data by reporting it as though the data came
from a normal distribution. Perhaps the simplest way to determine
whether a distribution is normal or log-normal is to transform the data
using the natural log and then use a goodness of fit test for the normal
distribution. A useful reference in this regards is R.B. D'Agostino and
M.A. Stephens: Goodness of Fit Techniques. Marcell Dekker, New York,
1986. Another good reference is LF Lacey et al: J Biopharmaceutical
Statistics 7, 171-178, 1997.
Hope this helps.
Peter L. Bonate, Ph.D.
Hoechst Marion Roussel
Clinical Pharmacokinetics
P.O. Box 9627 (F4-M3112)
Kansas City, MO 64134
fax: 816-966-6999
phone: 816-966-3723
--
X-Sender: jelliffe.-a-.hsc.usc.edu
Date: Mon, 20 Oct 1997 14:07:29 -0700
To: PharmPK.-a-.pharm.cpb.uokhsc.edu
From: Roger Jelliffe
Subject: Re: Median and Mean
Mime-Version: 1.0
Dear Yasuo:
Usually the median is better, as things are usually more symmetrically
distributed about it. Examples are the Vd of a drug when its distribution
is not Gaussian, and it hardly ever is. You might look at Dodge et al,
Population PK Models - Measures of Central Tendency, Drug Invest 5:
206-211, 1993. Hope this helps.
Roger Jelliffe
************************************************
Roger W. Jelliffe, M.D.
USC Lab of Applied Pharmacokinetics
CSC 134-B, 2250 Alcazar St, Los Angeles CA 90033
Phone (213)342-1300, Fax (213)342-1302
email=jelliffe.aaa.hsc.usc.edu
************************************************
Take a look at our Web page for announcements of
new software and upcoming workshops and events!!
It is http://www.usc.edu/hsc/lab_apk/
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To: PharmPK.at.pharm.cpb.uokhsc.edu
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From: "Steve Duffull"
Subject: Re: Median and Mean
Date: Tue, 21 Oct 97 16:55:09 PDT
It seems to me that the data will determine whether you use mean, median or
perhaps the mode to describe the central tendency of the distribution.
For the typical plasma profile, I think that it is often best just to show
just the individual's data. Often presenting the mean, or similar, will
hide interesting things in the conc-time profile such as secondary peaks
which may be due to enterohepatic cycling.
For PK population parameters, you should present the information that you
have for them. If you used a computer program that yielded the geometric
mean (and CV%) then this is what you should present. If, however, you used
a computer program that yielded the frequency histogram of the parameters
then it would seem appropriate to present the entire frequency histogram.
Presenting only the arithmetic mean and standard deviation implies that the
distribution of the parameter is Gaussian (which would need formal
testing). Presenting the median and quartiles (etc) does not describe the
distribution very well. Both parametric and nonparametric descriptions
will tend to hide interesting things in the distribution of the parameters,
eg subpopulations of patients that have different values (eg genetic
polymorphism).
I hope this helps.
Steve Duffull
=======================Steve Duffull
Christchurch
New Zealand
Ph +64 3 3815280
Fax +64 3 3640902
Email sduffull.-at-.clear.net.nz
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NONMEM, because it is an maximum likelihood method, reports the mode
for the population parameters. This is one reason that the
population estimates do not equate to the mean or median of the
individual estimates.
__________________________________________________
Leon Aarons
School of Pharmacy and Pharmaceutical Sciences
University of Manchester
Manchester, M13 9PL, U.K.
tel +44-161-275-2357
fax +44-161-275-2396
email l.aarons.-a-.man.ac.uk
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Yasuo,
If you want a simple answer to your simple question, it is median.
More detailed analysis, however, is required if the inter-individual
variability is extreemly large, as in case of polymorphic metabolism.
If the distribution of CL is actually bi- or polymodal you can hardly
find a unique parameter to represent a typical value.
How to do such analysis using minimal modelling assumptions? Suppose
(a rather typical example) you have many individual plasma
concentration-time profiles obtained at the same dosing regimen, and
individual sampling times are close to each other. Calculate medians
of individual measurements belonging to each sampling time cluster.
Then take ratios of measurements to the corresponding medians and plot
those ratios versus the individual sequential numbers. You will
immediately see the 'outlying' subjects which you have to analyse
separately from others. You may also pool all individual measurements
adjusted for sampling time-specific medians to get idea about the form
of overall concentration distribution (unimodal, polymodal, normal,
lognormal, etc.). This simple approach will help you to select an
appropriate way of further summarizing your PK data.
Regards,
Vladimir
--------
Vladimir Piotrovsky, Ph.D. Fax: +32-14-605834
Janssen Research Foundation Email: vpiotrov.-a-.janbe.jnj.com
Clinical Pharmacokinetics vpiotrov.-at-.janbelc1.ssw.jnj.com
B-2340 Beerse
Belgium
______________________________ Reply Separator
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Subject: Median and Mean
Author: PHARMPK (INTERNET.PHARMPK1) at SWIFTGATE
Date: 10/20/97 3:59 PM
PharmPK - Discussions about Pharmacokinetics
Pharmacodynamics and related topics
Dear readers,
Would anyone teach me which parameter, mean or median, is usually used in
evaluating the typical plasma profile and PK population parameters for the
data has the large inter-individual variability.
Thanks in advance.
Yasuo Koyama
koyamay.-at-.anet.ne.jp
Also see: http://www.cpb.uokhsc.edu/pkin/pkin.html
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)