title: Mass balance of 14C-bismuth sucrose octasulfate in Sprague-Dawley rats: evidence for dissociation of bismuth from sucrose octasulfate.
abstract: The mass balance of 14C bismuth sucrose octasulfate (BISOS) was investigated 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 experiment, bismuth was monitored in bile of bile-duct-cannulated animals for 48 h post-dose. Fecal excretion of bismuth averaged 95.8 +/- 5.30% bismuth dose, while 99.2 +/- 3.63% of the radiolabel was excreted in feces. Urinary excretion of bismuth averaged 0.051 +/- 0.028% bismuth dose, and 1.83 +/- 1.08% radioactive dose. Biliary excretion of bismuth averaged 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 limits. Though BISOS contains 57.3% by weight of bismuth, peak blood concentrations of bismuth were three orders of magnitude lower than for BISOS equivalents (Cmax for BISOS averaged 110 +/- 55.4 micrograms eq mL-1, while for bismuth it was 26.1 +/- 10.3 ng mL-1). This data indicates that bismuth dissociates from sucrose octasulfate, probably during the absorption phase, and exhibits differential pharmacokinetic characteristics from sucrose octasulfate. The low biliary and urinary excretion of both bismuth and BISOS equivalents is indicative of low systemic absorption. Greater than 96% recovery in feces, bile, and urine indicates that mass balance was achieved following oral administration.
authors.affiliation: Department of Clinical Pharmacokinetics, Hoechst Marion Roussel, Kansas City, MO 64134, USA.
authors.forename: N
authors.initials: N
authors.lastname: Rao
authors.forename: P W
authors.initials: PW
authors.lastname: Brown
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: T N
authors.initials: TN
authors.lastname: Thompson
authors.forename: J
authors.initials: J
authors.lastname: Geary
authors.forename: K W
authors.initials: KW
authors.lastname: Otis
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001646:Bile / Q000737:chemistry; D001729:Bismuth / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D014018:Tissue Distribution
chemical_list: D000897:Anti-Ulcer Agents; D002250:Carbon Radioisotopes; D013395:Sucrose; C053081:sucrose octasulfate; D001729:Bismuth