Document 0419
 DOCN  M9650419
 TI    Cationized hyperimmune immunoglobulins: pharmacokinetics, toxicity
       evaluation and treatment of human immunodeficiency virus-infected
       human-peripheral blood lymphocytes-severe combined immune deficiency
       mice.
 DT    9605
 AU    Pardridge WM; Kang YS; Diagne A; Zack JA; Department of Medicine,
       University of California at Los Angeles; School of Medicine, USA.
 SO    J Pharmacol Exp Ther. 1996 Jan;276(1):246-52. Unique Identifier :
       AIDSLINE MED/96135073
 AB    The in vivo pharmacokinetics and efficacy of cationized human
       immunoglobulins in the human-peripheral blood lymphocytes-severe
       combined immune deficiency mouse model were evaluated in the present
       studies using the severe combined immunodeficient mouse transplanted
       with human lymphocytes and infected with human immunodeficiency virus
       (HIV)-1. Immunoglobulins from noninfected humans and from HIV-infected
       individuals were cationized. The pharmacokinetic analysis showed that
       the cationized immunoglobulins have a markedly reduced mean residence
       time and a marked increase in organ uptake compared to the native
       immunoglobulins. The toxicity studies performed with homologous
       immunoglobulins in BALB/c mice demonstrated cationized homologous
       immunoglobulins have no tissue toxicity at a daily dose of 7.5 mg/kg.
       Treatment of HIV-infected severe combined immune deficiency mice that
       were transplanted with human lymphocytes demonstrated therapeutic
       efficacy for a 2-week treatment at a dose of 5 mg/kg cationized HIV
       immune globulin. In conclusion, cationized immunoglobulins are potential
       antibody-based therapeutics for the treatment of acquired immune
       deficiency syndrome; cationized antibodies undergo enhanced transport
       into lymphocytes and when homologous cationized immunoglobulins are
       administered there is no measurable tissue toxicity.
 DE    Animal  Antiviral Agents/*BLOOD/*PHARMACOLOGY/TOXICITY  Cations  Cells,
       Cultured  Female  Human  HIV Infections/*BLOOD/*DRUG THERAPY/IMMUNOLOGY
       HIV-1/*DRUG EFFECTS/PHYSIOLOGY  Immunoglobulins,
       Intravenous/*BLOOD/*PHARMACOLOGY/TOXICITY  Lymphocyte Transfusion
       Lymphocytes/DRUG EFFECTS/*VIROLOGY  Male  Mice  Mice, Inbred BALB C
       Mice, SCID  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Virus
       Replication/DRUG EFFECTS  JOURNAL ARTICLE

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