Pharmacokinetic analysis of biosynthetically radiolabeled mouse monoclonal antibodies in normal rhesus monkeys.
Two mouse monoclonal IgG2b antibodies that differ in their CH2 domains have been compared for their blood mean residence times (MRTs) in normal female Rhesus monkeys. A biosynthetically incorporated radiolabel (S-35 methionine) was used to follow blood elimination of the antibodies and urinary excretion. Results indicate that the blood (plasma) MRTs for the Ar13.4 and the ArM16.1 antibodies were remarkably similar in normal Rhesus monkeys. This observation varies greatly from those obtained with these same antibodies in separate studies in normal Balb/c mice. In Balb/c mice, the ArM16.1 antibody was found to be removed from the blood six times faster than the Ar13.4. The CONSAM program was used to fit a multiexponential function to the plasma data obtained from mice and monkeys. The sum of exponentials was then used to calculate the MRT values. These results demonstrate that mouse monoclonal antibody pharmacokinetics significantly differ between normal primates and mice. Presumably the Rhesus monkey better reflects the clinical behavior and pharmacokinetics of mouse monoclonal antibodies than do rodents. Therefore, the use of normal primates for the preclinical evaluation of monoclonal antibodies for in vivo use is suggested.
University of New Mexico College of Pharmacy, Immunopharmacology Laboratory, Albuquerque 87131.
S W
SW
Burchiel
R R
RR
Pollock
D G
DG
Covell
G
G
Fuller
M D
MD
Scharff
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D007700:Kinetics; D008253:Macaca mulatta; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G