PharmPK Discussion - Allometric scaling from animal to human with topical dosing

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On 20 Jun 2015 at 13:14:16, Thuy Hoang (thuy.hoang.aaa.UTEXAS.EDU) sent the message


We are developing a vaginal formulation in sheep and macaques and PK/PD data to inform the clinical
transition. What is the proper allometric scaling when working from sheep PK data and planning a
human study?

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On 20 Jun 2015 at 22:32:22, Conrad Housand (chousand.-at-.acslx.com) sent the message


Consider looking at the allometry methods described in the series of
articles published by the PhRMA CPCDC initiative on predictive models of
human pharmacokinetics (J Pharm Sci 2011).  If you have protein binding
info for humans and your preclinical species, methods are available to
improve CL and VDSS predictions relative to simple allometry.  If
absorption can be adequately modeled by a first order process, you might
be able to use the average of the absorption rate constant values
determined from preclinical species to predict the human value.  This is
how it¹s done in ADME Workbench.

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On 21 Jun 2015 at 12:20:23, Ronette Gehring (rgehring.-a-.ksu.edu) sent the message


Dear Thuy,

Whether the pharmacokinetics of a drug can be scaled using allometry, and
what the allometric exponent should be, varies by drug. You may find the
following publication useful. It looks at a wide range of species:

J Vet Pharmacol Ther. 2015 Jun;38(3):214-26. doi: 10.1111/jvp.12174. Epub
2014
Oct 21. Interspecies allometric meta-analysis of the comparative
pharmacokinetics of 85
drugs across veterinary and laboratory animal species. Huang Q(1), Gehring
R, Tell LA, Li M, Riviere JE.

Best regards,

Ronette

Ronette Gehring BVSc, MMedVet (Pharm), Dipl.ACVCP
Associate Professor: Department of Anatomy and Physiology
Institute of Computational Comparative Medicine
P217 Mosier Hall
Kansas State University
Manhattan, KS 66506

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