title: Further clinical studies of curdlan sulfate (CRDS)--an anti-HIV agent.
abstract: 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.
authors.affiliation: Aji Pharma USA, Inc., Glenpointe Centre West, Teaneck, NJ 07666, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gordon
authors.forename: M
authors.initials: M
authors.lastname: Guralnik
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Mimura
authors.forename: J
authors.initials: J
authors.lastname: Goodgame
authors.forename: W
authors.initials: W
authors.lastname: Lang
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D002850:Chromatography, Gel; D005936:Glucans / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count / Q000187:drug effects; D010314:Partial Thromboplastin Time; D047071:beta-Glucans
chemical_list: D000998:Antiviral Agents; D005936:Glucans; D047071:beta-Glucans; C063130:curdlan sulfate