Document 0424
 DOCN  M9650424
 TI    Further clinical studies of curdlan sulfate (CRDS)--an anti-HIV agent.
 DT    9605
 AU    Gordon M; Guralnik M; Kaneko Y; Mimura T; Goodgame J; Lang W; Aji Pharma
       USA, Inc., Glenpointe Centre West, Teaneck, NJ 07666,; USA.
 SO    J Med. 1995;26(3-4):97-131. Unique Identifier : AIDSLINE MED/96098544
 AB    Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide which
       inhibits the attachment of HIV to T-cells, and also has intracellular
       anti-HIV activity. In Phase I clinical trials, CRDS was found in 4 hr
       i.v. infusions, to be well tolerated up to 200 mg/70 kg and unexpectedly
       to produce marked, dose-related increases in CD4 lymphocytes in
       HIV-infected patients. Prolongation of bleeding time is expected to be
       the dose limiting toxicity, but no episodes of bleeding were seen. In
       one of the studies in this report, CRDS was administered i.v. daily for
       7 days to HIV patients at doses of 40, 100, 140 and 180 mg/70 kg/day. At
       the higher doses, marked increases in CD4 and CD8 lymphocytes were
       observed. These increases mainly returned to baseline after 24 hr. To
       further delineate the pharmacokinetics of these changes in CD4 and CD8
       lymphocytes, another Phase I study was done in which CRDS was infused
       i.v. over a 30 min period in HIV patients at single doses of 25, 50, 75,
       100, 125, 150, 175 and 200 mg/70 kg/day. The drug was well tolerated in
       all cases and marked increases in CD4 lymphocytes were again seen at the
       higher doses, in some cases amounting to increases of 500 cells/mm3
       after a single dose. The half-life of CRDS in man was found to be about
       two hours, as measured by activated partial thromboplastin time (APTT)
       and by plasma assays.
 DE    Antiviral Agents/ADMINISTRATION & DOSAGE/PHARMACOKINETICS/  *THERAPEUTIC
       USE  Chromatography, Gel  CD4 Lymphocyte Count/*DRUG EFFECTS
       CD4-Positive T-Lymphocytes/DRUG EFFECTS  CD8-Positive
       T-Lymphocytes/*DRUG EFFECTS  Glucans/ADMINISTRATION &
       DOSAGE/PHARMACOKINETICS/*THERAPEUTIC USE  Human  HIV Infections/*DRUG
       THERAPY/IMMUNOLOGY  Lymphocyte Count/DRUG EFFECTS  Partial
       Thromboplastin Time  CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  JOURNAL
       ARTICLE

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