Pharmacokinetic alteration in rats of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2.
We have investigated the pharmacokinetic alteration in rats of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2. Serum rIL-2 levels after the intravenous administration of the immune complex at a dose of 100 micrograms/rat as rIL-2 were significantly higher than those after intravenous administration of rIL-2 alone at the same dose. Pharmacokinetic analysis indicated that the distribution volume of rIL-2 decreased from 74.0 to 10.3 ml/rat, while the elimination rate of rIL-2 was little changed by immunocomplexing with the antibody. On the other hand, serum rIL-2 levels after the subcutaneous administration of the immune complex at a dose of 100 micrograms/rat as rIL-2 were sustained longer than those after the subcutaneous administration of rIL-2 alone at the same dose, and Tmax shifted from 0.83 to 3.0 h by immunocomplexing with the antibody. Pharmacokinetic analysis also revealed that the mean-residence-time of rIL-2 increased from 1.98 to 6.52 h, and the area-under-the curve of rIL-2 decreased slightly, from 834 to 548 ng.h/ml, by immunocomplexing with the antibody.
Sato
J
J
DDS Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Hamaguchi
N
N
Doken
K
K
Iwasa
S
S
Ogawa
Y
Y
Toguchi
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000936:Antigen-Antibody Complex; D002478:Cells, Cultured; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007376:Interleukin-2; D011994:Recombinant Proteins