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. 2002 Apr-Jun;27(2):101-5. doi: 10.1007/BF03190423.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / pharmacokinetics*
  • Endocytosis / physiology*
  • ErbB Receptors / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays / methods*

Substances

  • Antibodies, Monoclonal
  • ErbB Receptors