Monoclonal anti-epidermal growth factor receptor (ior EGF/r3) antibody pharmacokinetic studies on nude mice I: a radio-receptor analysis applied to drug serum quantification.
Due to its antagonistic properties upon ligand-epidermal growth factor receptor (EGFr) interaction, the monoclonal antibody anti-EGFr ior EGF/r3 is considered a potential therapeutic agent against several epithelium-derived tumours. This paper affords further analysis of the relevant corporal interaction of this monoclonal antibody in terms of its pharmacodynamic properties, using nude mice, following a single bolus intravenous dose administration. The radio-receptor assay allows quantification of the serum ior EGF/r3 level. The dose selection procedure, according to the Kolmogorov-Smirnov test, suggested using doses of 12.5-16 mg kg(-1) for pharmacokinetic assessments. The experimental data were best fitted to a bi-exponential function (r2 = 0.985), through the classical two-compartment open modelling approach. The model selection was corroborated by the AKAIKE information criteria, and also the SCHWARTZ and ESTRIP test were used. The estimated pharmacokinetic parameters (e.g. t 1/2 beta = 34.65 h, Vc = 2.84 mL, Vss = 4.21 mL and CL = 0.09 mL h(-1)) bear out the strategies for the evaluation of the therapeutic application of this drug. Finally, the radio-receptor analysis has provided a rationale for the proposed serum monoclonal antibody ior EGF/r3 quantification to characterize its concentration-time course.
Fernandez-Sánchez
E
E
Department of Pharmacology and Toxicology, Center of Biological Evaluation and Research, Institute of Pharmacy and Foods, University of Havana, La Coronela, Cuba.
Ducongé
J
J
Castillo
R
R
Garcia
I
I
Beausoleil
I
I
Macías
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics*; D066246:ErbB Receptors / Q000276:immunology*; D008297:Male; D051379:Mice; D008819:Mice, Nude
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors