Monoclonal anti-EGFreceptor antibody (ior-R3) pharmacokinetic study in tumor bearing nude mice: role of the receptor-mediated endocytosis on drug clearance.
With the purpose of describing the MAb ior-R3's kinetic behavior in disease state, this paper is focused on the study of this response using a human cancer (lung carcinoma cell line, H125) bearing nude mice animal model. This MAb was administered by a single 16 mg/Kg intravenous bolus dose and the blood samples were collected at several times ranging from 0 to 72 hours for serum drug quantification. The experimental data set was best fitted using a classical two-compartment mammilary pharmacokinetic (PK) model and the corresponding PK parameters were determined. Comparatively, the analysis of the more relevant physiologically-based PK parameters showed a significant enhancing of clearance as compound with the earlier reported study on healthy mice, increasing from 0.09 to 0.19 mL/h (p<0.01). However, the corresponding distribution volumes don't seem to be altered by the tumor xenograft. We conclude that all of these evidences suggest a possible mechanism of receptor-mediated endocytosis (RME) as a major cause of this increased drug clearance which also contributed to the faster decrease of the drug disposition.
Duconge
J
J
Department of Pharmacology and Toxicology, Center of Biological Evaluation and Research, Institute of Pharmacy and Foods, University of Havana, Cuba.
Fernández-Sánchez
E
E
Macías
A
A
Castillo
R
R
Garcia
I
I
Beausoleil
I
I
Amador
J F
JF
Matheu
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics*; D004705:Endocytosis / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors