Interspecies scaling of the monoclonal anti-EGF receptor ior EGF/r3 antibody disposition using allometric paradigm: is it really suitable?
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 differences of the ior EGF/r3 disposition behaviour among mammals.
Ducongé
Jorge
J
Laboratory of Biopharmaceutics, Department of Pharmacology, Institute of Pharmacy and Foods, University of Havana, Cuba. duconge@cieb.dld.cu
Fernández-Sánchez
Eduardo
E
Alvarez
Daniel
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D004285:Dogs; D004815:Epidermal Growth Factor / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D004815:Epidermal Growth Factor; D066246:ErbB Receptors