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Hi
We have need of some tissue information for physiological pk
modelling. Specifically we need tissue volumes and blood flow rates
in different animal species, but to begin with the rat would be fine.
We have mean values for this data but what we want is estimates of
variability (inter animal) and specifically covariance for this data.
What we would actually like is the raw data from which the means were
computed. Does anyone know of the availability of such data?
Thanks
Leon Aarons
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.aaa.man.ac.uk
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Here's a couple of references on parameter values for PBPK models:
Reference physiological parameters in pharmacokinetic modeling
US EPA EPA/600/6-88/004 February 1988
(reproduced by U.S. Department of Commerce, National Technical Information
Service, Springfield, VA 22161)
Physiological parameter values for PBPK models.
A report prepared by the International Life Sciences Institute, Risk Science
Institute under a cooperative agreement with the U.S. Environmental
Protection Agency, Office of Health and Environmental Assessment, December,
1994.
- Rory Conolly
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Dear Leon,
You can find the data you need on the following articles.
-B. Davies and T Morris Pharmaceutical Research 10 (7),1093/1095,
1993
-L.E.Gerlowsky and R.K.Jain J.Pharmaceutical Sci 72(10), 1103/1127, 1983
-Sakurada et al Am J Physiol 3, H59-66, 1978
Regards
Cristiana Morandini
Cristiana Morandini
Technologies Development Lab.
Bioanalysis and Drug Metabolism Dept.
GlaxoWellcome Research Center
Via Fleming 4 - 31135, Verona Italy
Phone: +39 45 9219102
Fax: +39 45 9218153
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Leon - Have you considered allometric relationships to model (or infer)
the covariance relationship between tissues in the rat? I am not aware of
publications that specifically express the variability of these
physiological/anatomical parameters. However, there is a large body of
information that shows how they are related to body weight. One might
model the variance as a function of body weight assuming a relatively
constant proportionality between the two, or incorporating some degree of
uncertainty for key tissues if you have data or a hypothesis to support
it.
Regards,
Jeff Wald
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Jeff
What we specifically need is the correlations between the different
tissues. This is never reported and that is why we probably need the
raw data.
Leon
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.at.man.ac.uk
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Leon
It would be nice to recommend my own publication on physiological
parameters, as others have done:
B. Davies and T Morris, Pharmaceutical Research 10 (7),1093/1095,
1993.
Unfortunately, Tim and I only gave single values for the parameters (and
have since been criticized for it). I do have some data on the variability
of certain physiological parameters and would be happy to share these data
if you let me know what it is you specifically want. The only other
publication that I know of that may help is:
R. Brown et al, Physiological parameter values for physiological based
pharmacokinetic models, Toxicol & Indust Health 1997, 13;407-484.
Regards
Brian
Advanced Biomedical Research, Inc.
Pennington, NJ 08534
609-818-1800
brian.davies.at.abr-pharma.com
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There was a poster by Tony Yates, Ivan Nestorov, and Malcolm Rowland
entitled, "Incorporating Measures of Variability and Uncertainty into
Interspecies Scaling of Human Pharmacokinetics," that was based on an
11-compartment whole body PBPK model. I'm sorry that I cannot recall
the exact meeting. It was presented a few years ago - Joyce
Joyce Mordenti, Ph.D.
Senior Director, Preclinical Sciences
Axys Pharmaceuticals, Inc.
650-829-1390; fax -1001
Joyce.-at-.axyspharm.com
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Leon
As far as I know there is no single source that can give you the information
you need. However there are a series of references from which you can glean
the information and maybe calculate parameters. Some of them give you blood
flow rates as a % of cardiac output etc. You can get Standard errors of
measurements for tissue weights and then get the density of the tissue from
another source and piece the info together. The references I am looking at
are:
1) Handbook of Laboratory Animal Science, Vol 3; Eds. Edward C. Melby,
Jr. and Norman H. Altman; CRC Press. 1976 (All laboratory animals)
2) Laboratory Animals, Vol. 27, pp 65-72, 1993 (Sprague-Dawley Rat
only)
3) Physiological parameter values for PBPK models.
A report prepared by the International Life Sciences
Institute, Risk Science
Institute under a cooperative agreement with the U.S.
Environmental
Protection Agency, Office of Health and Environmental
Assessment, December,
1994. (All laboratory animals)
4) Laboratory Animal Care, Vol. 19, p 746, 1969 (Long-Evans Rat)
5) Growth, Vol 36, pp 195-208, 1972 (Beagle Dog)
6) Toxicology and Applied Pharmacology; Vol. 6, pp 664-668, 1964
(Beagle Dog)
7) Toxicology and Industrial Health, Vol. 13, pp 407-484, 1997 (All
laboratory animals)
Hope this is helpful
Anup Zutshi Ph.D.
Pharmacokinetics and Metabolism
Pharmaceutical Product Development
Battelle Memorial Institute
Tel.No: (614) 424-5997
Fax: (614) 424-3268
E-Mail: zutshi.-a-.battelle.org
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Jeff, Leon, et al.:
I just recovered from the archive of PharmPK my old posting from
1998. (Re: [PharmPK Digest - Number 327])
I hope that it may help:
>>"Date: Fri, 20 Mar 1998 09:48:19 -0500
From: Janusz Byczkowski
To: PharmPK.at.pharm.cpb.uokhsc.edu
[...] The most complete source of data (known in the near Universe) is
published in a report:
Physiological Parameter Values for PBPK Models (R. Brown, Ed.). A
Report Prepared by the International Life Science Institute, Risk
Science Institute for US EPA in 1994, Washington, DC.
General estimates for the "hypothetical average representative rat"
in this report were derived from experimental mean values reported in
the literature:
From Table 2-5. Relative Organ weight (% Body Weight) in Rats
__________________________________________________________________
Organ Mean+_SD n of studies
________ ___________ ____________
Adipose Tissue - vary greatly, a very crude estimate (10%, or so)
Adrenals 0.019 +_0.007 7
Bone - vary greatly, a very crude estimate (7%, or so)
Brain 0.57 +_0.14 9
GI Tract
Stomach 0.46 +_0.06 4
Small Intestine 1.4 +_0.39 4
Large Intestine 0.84 +_0.04 4
Heart 0.33 +_0.04 9
Kidneys 0.73 +_0.11 12
Liver 3.66 +_0.65 15
Lungs 0.5 +_0.09 7
Muscle 40.43 +_7.17 2
Pancreas 0.32 +_0.07 3
Skin 19.03 +_2.62 5
Spleen 0.2 +_0.05 8
Thyroid 0.005+_0.002 3
___________________________________________________________
If you add these numbers you may account for about 85.5% of the total
body weight, so there is more than that (blood, claws, fur, stomach
and the intestine content, etc). [...]
Good luck,
Janusz Z. Byczkowski, Ph.D., D.Sc.>>
There was also an update of the reference:
>> [...] see article by: Brown RP, et al.
Physiological parameter values for physiologically based pharmacokinetic
models. Toxicol Ind Health. 1997 Jul; 13(4): 407-484...">>
Best wishes.
Janusz Z. Byczkowski, Ph.D.,D.Sc.,D.A.B.T.
Consultant
212 N. Central Ave.
Fairborn, OH 45324
voice (937)878-5531
office (614)644-3070
confidential fax (603)590-1960
e-mail januszb.-at-.AOL.com
homepage: http://members.aol.com/JanuszB/index.html
JZB Consulting web site: http://members.delphi.com/januszb/
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