Safety and pharmacokinetics: colloidal bismuth subcitrate.
Recent studies on oral administration of colloidal bismuth subcitrate suggest that, on average, the blood clearance of bismuth ranges from 50 to 95 ml/min, whereas the bioavailability of bismuth ranges from 0.16 to 0.28%. The higher values in each case assume that biliary clearance is a significant portion of the elimination, whereas the lower values assume only renal clearance. A minimal three-compartment model is necessary to describe the blood and urine excretion time-course data of bismuth. However, the intermediate half-life of 5-11 days represents most of the clearance and elimination. The Hillemand proposal that steady-state blood concentrations of greater than 50 ng/ml and greater than 100 ng/ml should be used as safety and alarm levels, respectively, for bismuth toxicity are probably overcautious, with little expectation of bismuth neurotoxicity associated with steady-state concentrations of 50-100 ng/ml. There is no clinical evidence to suggest that the transient high peak concentrations observed after oral doses of certain bismuth preparations are in any way related to toxicity. Pharmacokinetic theory suggests that initial high peak concentrations would result in only negligible increases in the predicted steady-state blood concentrations and steady-state amounts of drug in the body.
Benet
L Z
LZ
Dept. of Pharmacy, University of California, San Francisco 94143-0446.
D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D003102:Colloids; D006801:Humans; D009942:Organometallic Compounds / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D000897:Anti-Ulcer Agents; D003102:Colloids; D009942:Organometallic Compounds; C002791:bismuth tripotassium dicitrate