Orally administered dextran sulfate is absorbed in HIV-positive individuals.
Preliminary in vivo studies suggested that oral dextran sulfate was poorly absorbed, but investigations were limited by inadequate methods for measuring the drug in the body. To determine absorption in HIV-positive subjects, hydrogenated dextran sulfate, average molecular weight 8000 (Usherdex 8), was orally administered in a short-term (single dose, 4 g/day for 5 days, 7 subjects) and in a long-term study (1 g, 4 times per day for 29 to 335 days, 8 subjects), which was a continuation of the short-term study with the inclusion of an additional subject. When an agarose gel electrophoresis technique with toluidine blue staining was used, the drug was recovered from plasma (67%, peak 2.2 microg/mL) and circulating peripheral blood lymphocyte (PBL) samples (50%, peak 333 microg/L blood) obtained at 5 and 15 minutes and 1, 3, 6, and 24 hours after the first day's dose and from plasma (56%) and PBL samples (38%) obtained 5 minutes after administration on 4 subsequent days in the short-term study. In the long-term study, the drug was found in plasma (67%, peak 2.4 microg/mL) and PBL samples (25%, peak 126 microg/L blood) obtained at monthly visits within 4 hours of the last dose. The drug was found in all urine samples from all subjects in both studies (short-term study, 24-hour samples up to 4 days after the final dose; long-term study, monthly samples within 4 hours of the last dose). In the long-term study, bone marrow preparations from 3 subjects showed metachromatic inclusions present in reticular cells when the cells were stained with toluidine blue, indicating the presence of sulfated polyanions. A significant rise in activated partial thromboplastin time and a drop in platelet count (P < .025) were demonstrated, with thrombocytopenia developing in 3 patients. Mild-to-moderate gastrointestinal disturbances were experienced by 6 subjects in the short-term study and by all subjects in the long-term study. One subject experienced mild central nervous system symptoms in the short-term study. These results indicate that dextran sulfate is absorbed after oral administration; therefore, further studies on its efficacy, particularly in the early stages of the disease, along with additional observations on its toxicity, are warranted.
Hiebert
L M
LM
Department of Veterinary Physiological Sciences, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada.
Wice
S M
SM
Jaques
L B
LB
Williams
K E
KE
Conly
J M
JM
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D016516:CD4-CD8 Ratio / Q000187:drug effects; D016264:Dextran Sulfate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004587:Electrophoresis, Agar Gel; D006679:HIV Seropositivity / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male