Pharmacokinetics of bismuth and ranitidine following multiple doses of ranitidine bismuth citrate

1 The pharmacokinetics of bismuth and ranitidine derived from oral doses of ranitidine bismuth citrate 800  mg given twice daily for 28 days were examined in this double-blind, placebo-controlled, parallel-group study in 27 healthy subjects.
2 Bismuth accumulation in plasma reflected its multicompartmental disposition, achieving the majority of predicted steady state within 14–28 days. Bismuth absorption from ranitidine bismuth citrate is limited (<0.5% of the dose), and bismuth elimination is predominantly renal secretion. Peak plasma concentrations did not exceed 19  ng  ml⁻¹, remaining well below those associated with bismuth toxicity. Bismuth was measurable at low concentrations in plasma and urine for up to 5 months after the last dose. Plasma bismuth concentration-time data and urinary excretion data were best described by separate multicompartmental models, with terminal half-lives averaging 21 days and 45 days, respectively.
3 The pharmacokinetics of ranitidine derived from ranitidine bismuth citrate were similar to those of ranitidine administered alone. Ranitidine did not appreciably accumulate in plasma.
4 Ranitidine bismuth citrate was well-tolerated during 28 days of repeated dosing.