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

• Published in: Drugs in R&D Vol. 24; no. 1; pp. 81 - 87
• Main Authors: Luo, Hong-Yu, Xu, Shuo-Guo, Gao, Li-Chen, Long, Hui-Zhi, Zhou, Zi-Wei, Li, Feng-Jiao, Dai, Shang-Ming, Hu, Jin-Da, Su, Yu, Cheng, Yan
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2024; Springer Nature B.V; Adis, Springer Healthcare
• Subjects: Administration, Oral; Adult; Alcohol; Anticoagulants; Area Under Curve; Bismuth - administration & dosage; Bismuth - adverse effects; Bismuth - pharmacokinetics; Clinical trials; Drugs; Female; Healthy Volunteers; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Oral administration; Organometallic Compounds - administration & dosage; Organometallic Compounds - adverse effects; Organometallic Compounds - pharmacokinetics; Original; Original Research Article; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Potassium; Substance abuse treatment; Ulcers; Young Adult; China
• ISSN: 1174-5886; 1179-6901; 1179-6901
• DOI: 10.1007/s40268-024-00455-9

Background Potassium bismuth citrate is a gastric mucosal protector and a key drug for treating peptic ulcers. Objective To evaluate the pharmacokinetic characteristics and safety of 120-mg bismuth potassium citrate formulations administered orally under fasting conditions in healthy Chinese subjects. Method 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 ( C max ) and area under the curve concentration–time curve (AUC 0– t and AUC 0– ∞ ), and safety were evaluated via noncompartment analysis. Results The ratios of the least square geometric mean ratio between the test (T) and reference (R) formulations for C max , AUC 0– t , and AUC 0– ∞ 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. Conclusion 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.