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Hi group
I am working on gender-dependent toxicity of an insecticide. I
observe significant sex difference in in vitro metaboilsm. Sex
difference in in vivo toxicity (neurotoxicity) was evident beyond
certain dose i.e at slightly toxic dose, no difference, but at
moderately toxic dose, there is difference. My hypothesis is that the
sex difference is evident when the dose saturates the female's
capacity (i.e at vey high doses). I would like to conduct a
comparative study to see whether the absorption is different between
males and females to support my hypothesis.
My questions are
1. is my thinking right?
2. if i proceed with the absorption studies, what dose should I use,
non toxic dose or one of the toxic doses (slightly or moderately
toxic dose)?
3. if I use nontoxic dose to obtain absorption profile, can I use the
data to derive conclusion on the outcome of highly toxic dose?
any published references or documents are welcome
thanks in advance
satheesh
S. SATHEESH ANAND, Ph.D
Postdoctoral associate
Department of Pharmaceutical and Biomedical Sciences
College of Pharmacy
University of Georgia
Athens, GA-30602
TEl#706-542-5401
FAX#706-542-5358
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Hi Satheesh
I am not sure why you want to do absorption studies but here is what
I think you can do. Start by testing 3-4 doses:
- no toxicity,
- low toxicity,
- some toxicity in male, high toxicity in female, and
- high toxicity in both male and female
What you certainly should consider is to take PK samples so you can
establish a concentration-response (in this case toxicity)
relationship. Many people are content with dose-response findings but
if you have the means, it is much more informative if you have
concentration data. It seems that you have some in vitro data that
suggests saturable metabolism in female animals (what species?), so
what you need to show now is that this is true in an in vivo setting.
Once that is established (by looking at concentrations at different
doses), you can determine whether the differences in toxicity is due
to e.g. higher and persistent concentrations in female or if there is
a gender difference in the response to the substance.
Toufigh Gordi
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The following message was posted to: PharmPK
Dr. Anand,
A very general article on Gender-based differences is:
R. Czerniak, International J. of Tox., Vol 20, #3, 2001, ppg 161 - 163.
The entire proceedings of Symposium X of the 21st Annual ACT meeting,
Nov 2000 on Gender-based differences is covered in this vol, from pg 145
to 175.
Good luck,
Rick
Richard Czerniak, Ph.D.
Director Metabolism and Pharmacokinetics
Charles River Laboratories Preclinical Services
57 Union Street, Worcester, MA 01608
Phone: 508.890.0422
FAX: 508.753.1834
Pager: 877.708.6020
E-mail: richard.czerniak.-a-.us.crl.com
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