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The following message was posted to: PharmPK
We are currently involved in a project to model interindividual variation in
PBPK parameters that are a function of human physiology (organ volumes,
blood flows, cardiac output) for different age groups.
Can anyone direct us to a sources of data on the range and distribution of
values for these parameters in the general population or in specific
subpopulation? Data that link variation in parameter values to variation in
factors such as body weight (or BMI, lean body mass, sitting height, or
height) would be especially helpful. We would be glad to share the results
of our request with the list serv.
Paul S. Price
LINEA
Home Office
129 Oakhurst Rd.
Cape Elizabeth, ME 04107
Phone 1 207 799 3406
Fax 1 207 799 2529
psprice.-a-.pipeline.com
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The following message was posted to: PharmPK
Paul,
Estimates of the inter-individual variability for some parameters for
human PBPK models are available in the literature. References that
come to mind are:
Spear, R.C., Bois, F.Y. (1994). Parameter variability and the
interpretation of physiologically based pharmacokinetic modeling
results.Environmental Health Perspectives 102(11), 61-66.
Thomas, R.S., Bigelow, P.L., Keefe, T.J., Yang, R.S.H. (1996a).
Variability in Biological Exposure Indices using Physiologically-Based
Pharmacokinetic Modeling and Monte Carlo Simulation. American
Industrial Hygiene Association Journal 57, 23-32.
Thomas, R.S., Yang, R.S.H., Morgan, D.G., Moorman, M.P., Kermani,
H.R.S., Sloane, R.A., O'Connor, R.W., Adkins Jr, B., Gargas, M.L.,
Andersen, M.E. (1996). PBPK Modeling / Monte Carlo Simulation of
Methylene Chloride Kinetic Changes in Relation to Age and Acute,
Subchronic, and Chronic Inhalation Exposure. Environmental Health
Perspectives 104(8),858-865.
Delic, J.I., Lilly, P.D., MacDonald, A.J., Loizou, G.D. (2000). The
utility of PBPK in the safety assessment of chloroform and carbon
tetrachloride. Regulatory Toxicology and Pharmacology 32, 144-155.
The references below contain some information on associations between
parameters, such as cardiac output and BW or BSA.
Altman, P.L., Dittmer, D.S. (1971). Respiration and Circulation.
Federation of American Societies for Experimental Biology.
Fiserova-Bergerova, V. (1983). Modeling of Inhalation Exposure to
Vapors: Uptake, Distribution and Elimination. Volume II. CRC Press,
Inc., Florida.
Regards
Alex
Dr.A.J.MacDonald
Senior Scientist
Computational Toxicology Unit
Health and Safety Laboratory
Broad Lane
Sheffield
S3 7HQ
UK
Tel. +44 (0)114 2892902
Fax. +44 (0)114 2892500
email. Alex.MacDonald.-at-.HSL.gov.uk
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A good reference is the International Life Sciences Institute/Risk Sciences
Institute publication on "physiological parameter values for PBPK models".
It is available from ILSI at www.ilsi.org. You may need to contact them for
a photocopy (the document it is not hyperlinked directly). This document
provides a comprehensive review of parameter values from the literature and
also explores the relationship of these values to body weight. Another
source is Malcolm Rowland's PBPK resource in the UK which I believe provides
physiological values and is maintained by Ivan Nesterov.
Best Regards,
Robert Bies
Assistant Professor of Pharmaceutical Sciences and Psychiatry
Schools of Pharmacy and Medicine
University of Pittsburgh
Pittsburgh, PA, 15213
biesrr.-at-.msx.upmc.edu
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)