FURTHER CLINICAL-STUDIES OF CURDLAN SULFATE (CRDS) - AN ANTI-HIV AGENT

Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide whi ch inhibits the attachment of HIV to T-cells, and also has intracellul ar 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 unexpec tedly 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 f or 7 days to HIV patients at doses of 40, 100, 140 and 180 mg/70 kg/da y. At the higher doses, marked increases in CD4 and CD8 lymphocytes we re 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 infu sed i.v. over a 30 min period in HIV patients at single doses of 25, 5 0, 75, 100, 125, 150, 175 and 200 mg/70 kg/day. The drug was well tole rated 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/mm(3) after a single dose. The half-life of CRDS in man was foun d to be about two hours, as measured by activated partial thromboplast in time (APTT) and by plasma assays.