Summary
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. Comparativel, 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.
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Duconge, J., Fernández-Sánchez, E., Macías, A. et al. Monoclonal anti-EGFreceptor antibody (ior-R3) pharmacokinetic study in tumor bearing nude mice: Role of the receptor-mediated endocytosis on drug clearance. Eur. J. Drug Metab. Pharmacokinet. 27, 101–105 (2002). https://doi.org/10.1007/BF03190423
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DOI: https://doi.org/10.1007/BF03190423