M. Gordon et al., A PHASE-I STUDY OF CURDLAN SULFATE - AN HIV INHIBITOR - TOLERANCE, PHARMACOKINETICS AND EFFECTS ON COAGULATION AND ON CD4 LYMPHOCYTES, Journal of medicine, 25(3-4), 1994, pp. 163-180
Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide whi
ch has anti-HIV activity in vitro, and inhibits attachment of the viru
s to T-cells. After two weeks of exposure of virus and cells to CRDS,
there is complete inhibition of virus replication. CRDS is also active
against cytomegalovirus. The favorable toxicological profile of CRDS
in animals suggested clinical trials.In this study, doses of 0.014, 0.
14, 0.42, 1.42, 2.84 and 4.26 mg/Kg (hereinafter referred to as 1, 10,
30, 100, 200 and 300 mg/body, respectively, for convenience) were adm
inistered to three HIV-positive patients at each dose level for four h
ours intravenously. Activated partial thromboplastin times (APTT) were
measured hourly. Unexpectedly, single doses of CRDS produced marked,
dose-related, increases in CD4 lymphocytes in HIV-infected patients. T
here were no clinical side effects seen at any dose tested. All labora
tory parameters were normal except for prolongation of APTT in the 200
and 300 mg dose group. Two patients in the 300 mg dose group had a do
ubling of the APTT during the four hour infusion, which was the termin
ation point of the trial according to the protocol. The half-life of C
RDS was estimated to be 2 to 3 hours from the APTT data and from the b
lood level assays (not shown). CRDS was well tolerated in the study wi
th the APTT levels being a convenient monitoring basis for dosing. Mar
ked increases in CD4 levels were seen at higher doses, which, if confi
rmed and extended, may have therapeutic implications. CRDS is consider
ed safe for multiple dosing with monitoring of APTT.