MASS-BALANCE OF C-14 BISMUTH SUCROSE OCTASULFATE IN SPRAGUE-DAWLEY RATS - EVIDENCE FOR DISSOCIATION OF BISMUTH FROM SUCROSE OCTASULFATE

The mass balance of C-14 bismuth sucrose octasulfate (BISOS) was inves tigated in eight male Sprague-Dawley rats after single oral doses of 1 .0 g kg(-1). Bismuth and radioactivity were monitored in blood, urine, and feces for up to 144 h post-dose, while kidneys, brain, liver, and lungs were assayed for bismuth at 144 h post-dose. In a separate expe riment, bismuth was monitored in bile of bile-duct-cannulated animals for 48h post-dose. Fecal excretion of bismuth averaged 95.8+/-5.30% bi smuth dose, while 99.2+/-3.63% of the radiolabel was excreted in feces . Urinary excretion of bismuth averaged 0.051+/-0.028% bismuth dose, a nd 1.83+/-1.08% radioactive dose. Biliary excretion of bismuth average d 0.0003+/-0.0006% bismuth dose, and 0.026+/-0.030% radiolabeled dose. An average 0.005+/-0.002% of the bismuth dose was present in kidney, liver, and lung. Bismuth levels in brain were below quantifiable limit s. Though BISOS contains 57.3% by weight of bismuth, peak blood concen trations of bismuth were three orders of magnitude lower than for BISO S equivalents (C-max for BISOS averaged 110+/-55.4 mu g eq mL(-1), whi le for bismuth it was 26.1+/-10.3 ng mL(-1)). This data indicates that bismuth dissociates from sucrose octasulfate, probably during the abs orption phase, and exhibits differential pharmacokinetic characteristi cs from sucrose octasulfate. The low biliary and urinary excretion of both bismuth and BISOS equivalents is indicative of low systemic absor ption. Greater than 96% recovery in feces, bile, and urine indicates t hat mass balance was achieved following oral administration. (C) 1997 John Wiley & Sons, Ltd.