Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. First communication: plasma concentration, distribution, metabolism and excretion of the new monoclonal antibody, regavirumab after intravenous administration in rats and rabbits.
TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The pharmacokinetics of MCA C23 was investigated in rats and rabbits. Plasma concentrations of radioactivity were shown to increase dose-dependently after 2, 10 or 50 mg/kg of 125I-labeled TI-23 was administered intravenously to rats. Their elimination of half-lives from plasma were 11-13 days. The radioactivity in plasma corresponded with the idiotype activity (antigenicity against idiotype antibody) of the monoclonal antibody. No significant difference was detected in plasma concentration and half-lives between male and female rats. Quantitative and qualitative distribution studies demonstrated that high radioactivity was distributed predominantly to the blood and blood-rich organs. The idiotype activity which remained in those tissues was attributable to the blood in the tissues. The radioactivity was mainly excreted in the urine as free iodine, and about 40% of the dose remained in the body. After the rabbits received 2 mg/kg of 125I-TI-23, the initial radioactivity in plasma was higher than in rats, and a larger distribution volume and shorter elimination half-lives of radioactivity in plasma were observed.
Arizono
H
H
Pharmacological Research Department, Teijin Institute for Bio-Medical Research, Teijin Limited, Tokyo, Japan.
Ishii
S
S
Nagao
T
T
Kudo
S
S
Sasaki
S
S
Kondo
S
S
Kiyoki
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001345:Autoradiography; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003587:Cytomegalovirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*; D013045:Species Specificity; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007457:Iodine Radioisotopes; D012709:Serum Albumin; C089553:TI-23 human monoclonal antibody; D005998:Glycine