Pharmacokinetics of an HIV-1 gp120-specific chimeric antibody in patients with HIV-1 disease.
The pharmacokinetics of mouse V/human C (gamma 1, kappa) chimeric monoclonal antibody CGP 47 439 specific for the principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) was studied in patients with stage IV HIV-1 disease in an open-labeled phase I/IIA trial. Twelve male patients were enrolled and nine completed the study. Patients were divided into three groups according to the extent of CGP 47 439 to bind to gp120 from their viral isolates: undetectable for group 1, modestly reactive for group 2, and strongly reactive for group 3. A first dose of 1, 10, or 25 mg was administered by intravenous infusion to group 1, group 2 and group 3 patients, respectively. The patients then received seven doses of 50, 100, or 200 mg, respectively, every three weeks. CGP 47 439 serum concentrations were determined by an ELISA using monoclonal antibody AB19-4 specific for the idiotope of CGP 47 439. Half an hour after infusion only 25.5-36.1% of the administered antibody was found in the serum, reflecting its rapid distribution in the extravascular space and possibly binding to gp120 antigen in some of the patients. The terminal elimination half-life (T1/2) was 16.2 days in group 1 patients, 9.7 days in group 2 and in group 3 patients 7.5 days and 9.1 days. An antibody response to CGP 47 439 was not a factor in determining elimination rates, because only very low and transient responses were found in three patients. These results suggest that the reactivity of CGP 47 439 with HIV-1 gp120 contributed to its elimination in HIV-1 infected patients.
Schüpbach
J
J
Swiss National Center for Retroviruses, University of Zürich.
Günthard
H
H
Fung
M S
MS
Liou
R S
RS
Botta
L
L
Gowland
P
P
Gordon
W
W
Gygax
D
D
Chang
N T
NT
Chang
T W
TW
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood* / Q000235:genetics; D015483:HIV Antibodies / Q000008:administration & dosage / Q000097:blood / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011993:Recombinant Fusion Proteins