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The following message was posted to: PharmPK
Hi
I wanted to see if anyone in this discussion group has experience in
doing gene expression investigations in the context of PK or PD studies
in human. During such studies, we can obtain blood mononuclear cells
say before dose and at Tmax which can generate mRNA for Array analysis
or rtPCR but the question is what is the degree of correlation between
gene expression on mononuclear cells with hepatic and/or intestinal
gene expression? Also does one given dose under either single dose or
steady state condition, can cause detectable alteration in the
expression of genes responsible for drug metabolizing enzymes,
transporters and/or effects?
I would really appreciate if you could share any information you may
have on such studies.
Many thanks
Fatemeh Akhlaghi, PharmD, PhD
Assistant Professor
Biomedical and Pharmaceutical Sciences (BPS)
University of Rhode Island
125 Fogarty Hall, 41 Lower College Road
Kingston, RI 02881
USA
Phone: (401) 874 9205
Fax: (401) 874 2181
Email: fatemeh.-at-.uri.edu
Laboratory Website:
http://www.uri.edu/pharmacy/faculty/aps/akhlaghi/index
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The following message was posted to: PharmPK
Fatemeh,
There are many studies reported in the literature concerning
inducibility of CYP1A1 in leucocytes, and presumably this could be
used as a surrogate for hepatic CYP1A2 induction. Unfortunately,
although low levels of CYP3A are detectable in leucocytes it is not
inducible there, presumably because the cells do not express PXR.
I hope that this helps.
All the very best,
Bernard
--
Bernard Murray, Ph.D.
Senior Research Investigator
Drug Metabolism, PCS, PPD, GPRD, Abbott Laboratories, Chicago, USA
Bernard.Murray.at.abbott.com
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)