       Document 0757
 DOCN  M9640757
 TI    The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in
       patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials
       Group (ACTG) of the National Institute of Allergy and Infectious
       Diseases.
 DT    9604
 AU    Tierney M; Pottage J; Kessler H; Fischl M; Richman D; Merigan T;
       Powderly W; Smith S; Karim A; Sherman J; et al; Massachusetts General
       Hospital, Boston 02114, USA.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Dec 15;10(5):549-53.
       Unique Identifier : AIDSLINE MED/96142217
 AB    Twenty-nine patients were enrolled in a phase I dose-escalating
       tolerance trial of N-butyl-deoxynojirimycin, an alpha-glucosidase I
       inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication
       by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and
       subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum
       tolerated dose was not achieved because of slow accrual and because the
       study was stopped after the finding of cataracts in initial long-range
       rat toxicology studies. These cataracts were later shown to be transient
       and not found in other animals. The most common side effects were
       gastrointestinal, with diarrhea and flatulence occurring in most
       subjects, which seemed to partially improve on a modified diet that
       excluded complex carbohydrates. Grade III elevations in liver function
       tests were seen in two patients. Grade III leukopenia and neutropenia
       were seen in seven patients, but were only severe enough in two to
       require discontinuation. No significant trends in CD4 cell counts or
       HIV-1 p24 levels were noted.
 DE    Adult  Animal  Antiviral Agents/ADVERSE EFFECTS/*PHARMACOKINETICS
       Cataract/CHEMICALLY INDUCED  CD4 Lymphocyte Count  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  Diarrhea/CHEMICALLY INDUCED  Female
       Flatulence/CHEMICALLY INDUCED  Half-Life  Human  HIV Core Protein
       p24/ANALYSIS  HIV Infections/IMMUNOLOGY/*METABOLISM  *HIV-1  Lens,
       Crystalline/DRUG EFFECTS  Leukopenia/CHEMICALLY INDUCED  Liver/DRUG
       EFFECTS  Male  Neutropenia/CHEMICALLY INDUCED  Rats
       1-Deoxynojirimycin/*ANALOGS & DERIVATIVES/ADVERSE EFFECTS/
       PHARMACOKINETICS  CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  JOURNAL
       ARTICLE  MULTICENTER STUDY

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

