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Dear all,
The liver blood flow is an important parameter in particular in the
understanding of clearance , bioavailability and also for scaling up
in-vitro intrinsic clearance. Despite numerous articles on the subject
(Davies and Morris, 1993 perhaps being the most cited) there appears
from the recent literature to be still some significant discrepancies
in the standard values used between pharmaceutical companies. At the
moment our Department is using the following values (all in mL/min/kg):
Mouse 90
Rat 85
Dog 31
Cyno 44
Marmoset 60
Human 21
It would be interesting to hear other opinions and in particular the
basis for the choice. In addition Rhesus monkey is a species commonly
used for PET studies, however I have not seen any references refering
to the liver blood flow of this species.
Best regards
Bob Barnaby
GSK
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Robert (and all):
One of the very important factors to take into account is the
physiological status of the subject. Let me give you one illustrative
example:
Several years ago, as we were starting to measure tumoral PK/PD, we had
a patient with Breast CA, where we did both tumoral PK (using 19F-MRS)
and tumoral perfusion measurements, using Dynamic Contrast Enhanced MRI
(DEMRI), at the beginning of her month long infusion study, and at the
end.
Both studies were done late afternoon, as we wanted to avoid any
circadian variations. When she came back for her second study patient
SV136 was much more animated, which we assumed was due to the
satisfaction of the end of treatment. When, however, we realized that
the ICAR (Initial Contrast Accumulation Rate) of her non-diseased liver
had shot up from 4.9 to 10.9 (relative units) [an increase of 122%],
whereas the ICAR of her central blood pool had only increase from 168
to 201 (~20%, within the limits of allowed hemodynamic variability). It
turned out that she had celebrated with her family the end of the
infusion treatment, before coming to the MRI, and hence was in a full
post-absorptive phase.
Needless to say, our protocols since include a strict rule of NPO for 3
hrs before the DEMRI study.
Hence, your question below needs to include a definition of
physiological conditions, where food intake is only one of the
variables.
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-.usc.edu
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