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Pharmacokineticists and others interested in physiological modelling
need accurate reference values for including in their models - blood
flows to organs, weights of organs, normal contents of cells,
metabolising enzymes etc.
My question is this: where do you go to find such authoritative,
accurate, up-to-date information. The question is very open ended
and may be a standard reference book, an Internet website, a
colleague, or your own records.
As this is in the nature of a survey as well as a request for
information, I would be grateful for a one-line reply from everyone,
even if the answer is likely to be duplicated.
I look forward to lots of replies (Please reply directly to me at
spiresgate.-at-.aol.com).
Joe Chamberlain
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The following message was posted to: PharmPK
Joe:
You raise an interesting question that can today be answered in a manner
that is very different from what it was only a few years ago.
Taking your first item: blood flow to organs, that can be measured, as
we and others have shown, using Dynamic Enhanced MRI (DEMRI) methods to
measure, directly, the rate of proton enhancement in tissues and organs,
a parameter that is proportional to the blood flow to that organ in THAT
patient at THAT particular state of his/her disease. Blood flow to
organs and tissues varies significantly, not only with the status of the
tissue, but also with the nutritional status of the subject and on other
regulatory aspects of human physiology.
That is why I feel that proper modelling requires direct data from the
individual being studied, rather than only general statistical
information. The old cartoon from Remington comes always back to my
mind: there are two bullet holes, one to the right and one to the left
of the duck. The legend says: statistically, the duck is dead.
The use of noninvasive methods in drug monitoring, and in physiological
monitoring, was summarized last year in the April 15, 2000 issue of
Advanced Drug Delivery Reviews (41/1).
Professor Walter Wolf, Ph.D.
Distinguished Professor of Pharmaceutical Sciences
Director, Pharmacokinetic Imaging Program
Department of Pharmaceutical Sciences, School of Pharmacy
University of Southern California
1985 Zonal Ave., Los Angeles, CA 90089-9121
E-Mail: wwolfw.-at-.hsc.usc.edu
Telephone: 323-442-1405
Fax: 323-442-9804
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Joe:
Some time ago, I wrote to this list:
"...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..."
You may find there normal physiological values for most of the
laboratory animals and for humans (except, contents of cells and
metabolizing enzymes). It has been published since in a peer reviewed
journal, Toxicology and Industrial Health in 1997.
Reference:
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
FAX (208)330-9302
e-mail januszb.at.AOL.com
homepage: http://members.aol.com/JanuszB/index.html
JZB Consulting web site: http://members.aol.com/JanuszB/consult.htm
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The following message was posted to: PharmPK Joe,
The answer to your question is: you go to the literature, you talk to
people in the industry and in academia who conduct relevant research,
and you divine some of it through a synthesis of the other
information you obtain. This is a very tedious process. We have spent
a number of person-years collecting and analyzing such information.
I would suggest that for people to do your homework and send you a
personal reply is not in tune with the intent of this forum. Rather,
replies should be public so that all can benefit from such shared
information.
To start, I will refer you to a comprehensive review coming out soon
in a special edition of Advanced Drug Delivery:
Agoram, Woltosz, and Bolger, "Predicting the impact of physiological
and biochemical processes on oral drug bioavailability"
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The following message was posted to: PharmPK
Joe... one reference I have seen used is as follows:
Physiologic parameters in laboratory animals and humans.
Davies B. and Morris T. Pharmaceutical Research, 10(7): 1093-1095, 1993.
Best Regards,
Christopher S. Lepsy, Ph.D.
Pharmacokinetics, Dynamics, and Metabolism Department
Pfizer Global Research and Development
Ann Arbor Research Laboratories
2800 Plymouth Rd. , Ann Arbor, MI 48105
christopher.lepsy.-a-.pfizer.com
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)