Dear friends,Back to the Top
I would like to ask your opinion on the preferred animal model to use
for comparing preliminary/exploratory drug formulations with respect to
assessment of oral bioavailability: rats vs. dogs.
A few 'technical' arguments in favor of one vs. the other are quite
clear such as the cost (dogs>rats), crossover design not possible in
rats. Therefore, please refer to the scientific aspects such as the
correlation with bioavailability in humans, physiological/anatomical
aspects and any other technical aspects. References are most welcomed!
Thank you
ES
About comparisons of preclinical species prediction of humanBack to the Top
pharmacokinetics excellent articles are available: two by K. W. Ward
and B.R Smith and one by R. Scott Obach and al.
Keith W. Ward and Brian R. Smith
A COMPREHENSIVE QUANTITATIVE AND QUALITATIVE EVALUATION OF
EXTRAPOLATION OF INTRAVENOUS PHARMACOKINETIC PARAMETERS FROM RAT, DOG,
AND MONKEY TO HUMANS. I. CLEARANCE
Drug Metab Dispos 2004 32: 603-611.
Keith W. Ward and Brian R. Smith
A COMPREHENSIVE QUANTITATIVE AND QUALITATIVE EVALUATION OF
EXTRAPOLATION OF INTRAVENOUS PHARMACOKINETIC PARAMETERS FROM RAT, DOG,
AND MONKEY TO HUMANS. II. VOLUME OF DISTRIBUTION AND MEAN RESIDENCE
TIME
Drug Metab Dispos 2004 32: 612-619.
R. Scott Obach, James G. Baxter, Theodore E. Liston, B. Michael Silber,
Barry C. Jones, Fiona Macintyre, David J. Rance, and Philip Wastall
The Prediction of Human Pharmacokinetic Parameters from Preclinical
and In Vitro Metabolism Data
J Pharmacol Exp Ther 1997 283: 46-58.
Best regards
Stefano Porzio
Pharmacokinetic and Tox. Dept.
Inpharzam Ricerche SA - ZAMBON-GROUP
Taverne - Switzerland
Dear ErnestBack to the Top
A good reference for physiological differences between species is:
Anatomical and physiological differences between various species used
in studies on the pharmacokinetics and toxicology of xenobiotics. A
review of literature RIVM Rapport 623860010
Zwart LL de ; Rompelberg CJM ; Sips AJAM ; Welink J ; Engelen JGM van
Available at http://www.rivm.nl/bibliotheek/rapporten/623860010.html
You should also take into account the pharmacological properties of
your drug to select the best species, ie dogs are well-known to be very
sensitive to emetic effects.
Regards,
Antoine DESLANDES
Gencell SAS
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