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M9650419.TXT
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1996-03-09
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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).