       Document 0963
 DOCN  M9440963
 TI    Pharmacokinetics of an HIV-1 gp120-specific chimeric antibody in
       patients with HIV-1 disease.
 DT    9404
 AU    Schupbach J; Gunthard H; Fung MS; Liou RS; Botta L; Gowland P; Gordon W;
       Gygax D; Chang NT; Chang TW; et al; Swiss National Center for
       Retroviruses, University of Zurich.
 SO    Biotherapy. 1993;6(3):205-15. Unique Identifier : AIDSLINE MED/94122031
 AB    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.
 DE    Adult  Antibodies, Monoclonal/ADMINISTRATION & DOSAGE/*BLOOD/GENETICS
       Human  HIV Antibodies/ADMINISTRATION & DOSAGE/BLOOD/*GENETICS  HIV
       Envelope Protein gp120/GENETICS/*IMMUNOLOGY  HIV
       Infections/BLOOD/*IMMUNOLOGY  *HIV-1  Infusions, Intravenous  Male
       Middle Age  Recombinant Fusion Proteins/IMMUNOLOGY/*PHARMACOKINETICS
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

