Interspecies scaling of the monoclonal anti-EGF receptor ior EGF/r3 antibody disposition using allometric paradigm: is it really suitable?
✍ Scribed by Jorge Ducongé; Eduardo Fernández-Sánchez; Daniel Alvarez
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 139 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0142-2782
- DOI
- 10.1002/bdd.398
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✦ Synopsis
Abstract
The pharmacokinetic regularity of the murine monoclonal antibody ior EGF/r3 across mammals was studied using allometry. The allometric relationship between the volume of distribution and body weight (W) across mammalian species was characterized by the power equation V~d~=218.8 W^0.84^ (r=0.92), and that for clearance by CL=2.96 W^0.76^ (r=0.97, excluding the dog). The complex Dedrick plot of the ior EGF/r3 pharmacokinetic data produced a superimposable profile (r=0.73). However, a 4‐fold variation was observed between the expected human ior EGF/r3 clearance and the cancer patients' values, using apolysichron time units. The patients showed clearance values that overreached the prediction, and the neoteny phenomena cannot explain such a difference. The pharmacokinetic data from cancer patients, rather than healthy volunteers, suggested any tumour‐associated drug clearance process as a possible determinant of the mentioned underestimation. Finally, the results obtained in this study confirmed the potential use of allometric scaling to obtain more insight into the similarities and/or differenhyphences of the ior EGF/r3 disposition behaviour among mammals. Copyright © 2004 John Wiley & Sons, Ltd.