Pharmacokinetic and Safety Study of Bismuth Potassium Citrate Formulations in Healthy Subjects

Potassium bismuth citrate is a gastric mucosal protector and a key drug for treating peptic ulcers. To evaluate the pharmacokinetic characteristics and safety of 120-mg bismuth potassium citrate formulations administered orally under fasting conditions in healthy Chinese subjects. A single-center open two-cycle trial was conducted on 12 healthy subjects who received a single oral dose of 120 mg of bismuth potassium citrate. The plasma concentration of bismuth was determined using a validated inductively coupled plasma mass spectrometry (ICP‒MS) method. The pharmacokinetic parameters, including maximum serum concentration (Cmax) and area under the curve concentration–time curve (AUC0–t and AUC0–∞), and safety were evaluated via noncompartment analysis. The ratios of the least square geometric mean ratio between the test (T) and reference (R) formulations for Cmax, AUC0–t, and AUC0–∞ were 44.8%, 55.5%, and 64.4%, respectively; the bilateral 95% confidence intervals (Cis) for these parameters were 20.2–99.6%, 24.1–127.5%, and 23.7–175.0%, respectively, and the non-inferior limits for these parameters were 169.4%, 198.8%, and 200.5%, respectively. The upper limits of the one-sided 97.5% confidence interval for the least squares geometric mean ratio (T/R) were lower than the non-inferior limits. No serious adverse reactions or adverse reactions leading to detachment were observed among the subjects. The concentration of bismuth in the blood of healthy subjects in the T formulation was not greater than that in the R formulation. Similarly, the safety of oral administration of 120 mg of bismuth potassium citrate formulations to healthy subjects was good. The trial registration number (TRN) was [2018] 013, 6 December 2018.