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 measuri ng the drug in the body. To determine absorption in HIV-positive subjects, hydrogenated dextran sulfate, average molecular weight 8000 (Usherdex 8), w as 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 in clusion of an additional subject. When an agarose gel electrophoresis techn ique with toluidine blue staining was used, the drug was recovered from pla sma (67%, peak 2.2 mu g/mL) and circulating peripheral blood lymphocyte (PB L) samples (50%, peak 333 mu g/L blood) obtained at 5 and 15 minutes and 1, 3, 6, and 24 hours offer 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 pla sma (67%, peak 2.4 mu g/ml) and PBL samples (25%, peak 126 mu g/L blood) ob tained at monthly visits within 4 hours of the last dose. The drug was foun d 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, monthl y samples within 4 hours of the last dose). In the long-term study, bone ma rrow preparations from 3 subjects showed metachromatic inclusions present i n reticular cells when the cells were stained with toluidine blue, indicati ng the presence of sulfated polyanions. A significant rise in activated par tial thromboplastin time and a drop in platelet count (P < .025) were demon strated, with thrombocytopenia developing in 3 patients. Mild-to-moderate g astrointestinal disturbances were experienced by 6 subjects in the short-te rm study and by all subjects in the long-term study. One subject experience d mild central nervous system symptoms in the short-term study. These resul ts indicate that dextran sulfate is absorbed after oral administration; the refore, further studies on its efficacy, particularly in the early stages o f the disease, along with additional observations on its toxicity, are warr anted.