Abstract

Background: The mucosal protective agent, bismuth potassium citrate, is used for treatment of chronic gastritis and gastric stress conditions, including heartburn and acid reflux.
Objectives: 1) To establish and validate a new inductively coupled mass spectrometry (ICP-MS) analytical method for the determination of bismuth metal in human plasma; and 2) to determine the systemic absorption and safety characteristics of bismuth following the administration of bismuth potassium citrate granules (test drug) and bismuth potassium citrate tablets (reference drug) in healthy Chinese subjects.
Materials and methods: A single-center, randomized, open-label, two-drug, single-dose, two-cycle, double-crossover pharmacokinetics study was carried out in a cohort of 24 healthy adult subjects in the fasting state. Subjects meeting the inclusion criteria were randomly assigned to the first cycle in ascending order of screening number obtained prior to dosing. The randomization table assigned subject either to the TR-group (test-reference cycle) or the RT group (reference-test cycle) where each group contained a total of 12 subjects. Subjects recruited but not completing the study, or in whom the data sets were incomplete, were not replaced. Using this study design, all subjects received a single dose of both preparations in the fasting state whereby 12 subjects received the drugs in the order RT and 12 subjects in the order TR, with a washout period of 7 days between each drug administration cycle, respectively.
Results: Pharmacokinetic parameters (concentration maximum (C_max), AUC_0–t, and area under the concentration-time curve to infinity (AUC_0–∞) were analyzed using a linear mixed-effects model after natural log transformation. The lower limit of the 90% confidence intervals for the geometric mean ratio (test preparation/reference preparation) were below 100%, and the bioavailability of the test formulation (granules) was markedly superior to that for the reference formulation (tablets) where values for C_max, AUC_0–t, and AUC_0–∞ after natural log transformation were 5.44, 12.82, 10.86, 22.44, and 13.79%, 27.42%, respectively. The systemic absorption of bismuth metal from the granules was not greater than that for the tablets.
Conclusion: Although the bioavailability of the granules was markedly superior to tablets, the systemic absorption of bismuth metal from the two formulations was similar, and there was no evidence for a difference in the safety characteristics.

Author Details

Authors

• Xiaozhi Lv¹
• Junyan Wu¹
• Suiwen Ye¹
• Quansheng Wang²
• Shuguang Gan²
• Jianbin Pi²
• Yongjian Xiong²
• Nan Zhang¹

Departments

• ¹ SUP Phase I Clinical Trial Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yuexiu District, Guangzhou, and
• ² Hubei Huquan Pharmaceutical Co., Ltd., Wuhan City, Hubei Province, China

Address

Junyan Wu
or
Suiwen Ye
SUP Phase I Clinical Trial Centre
Sun Yat-sen Memorial Hospital
Sun Yat-sen University
No. 107 Yanjiang West Road,
Yuexiu District, Guangzhou 510120, China
Email: [email protected]; [email protected]

Citation