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Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial

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Abstract

Background

Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects.

Methods

An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14–20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21–27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period.

Results

The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration–time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52–218.71%) and 287.54% (263.28–314.04%) for tegoprazan and 423.23% (382.57–468.22%) and 385.61% (354.62–419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44–90.45%) and 110.30% (102.74–118.41%) for clarithromycin, 126.25% (114.73–138.93%) and 146.94% (135.33–159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73–82.60%) and 94.34% (87.94–101.20%) for amoxicillin, and 158.43% (125.43–200.11%) and 183.63% (156.42–215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages.

Conclusion

The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability.

Clinical Trials Registration

CTR20230643.

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Author notes

  1. Yujing Du and Lixiu Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, Hubei, China

    Yujing Du, Lixiu Yu, Bin Deng, Qinying Li, Junrui Hu, Linjie Li, Yusen Xu, Xuejia Zhai & Yongning Lu

  2. Hubei Province Clinical Research Centre for Precision Medicine for Critical Illness, Wuhan, 430022, Hubei, China

    Lixiu Yu, Bin Deng, Xuejia Zhai & Yongning Lu

  3. Shandong Luoxin Pharmaceutical Group Co., Ltd, Linyi, 276017, Shandong, China

    Liangwei Song, Fang Xie, Yinghui Wang, Yuhao Chen & Chengxin Liu

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  1. Yujing Du
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Corresponding authors

Correspondence to Xuejia Zhai or Yongning Lu.

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Funding

This work was supported by the Key Research and Development Plan of Hubei Province, China (2023BCB030) and the Chinese Pharmaceutical Association (CPA-Z05-ZC-2022-002). The study was also supported by Shandong Luoxin Pharmaceutical Group Co., Ltd.

Conflict of Interest

Liangwei Song, Fang Xie, Yinghui Wang, Yuhao Chen, and Chengxin Liu are employees of Shandong Luoxin Pharmaceutical Group Co., Ltd. They have no other relevant disclosures to declare. Yujing Du, Lixiu Yu, Bin Deng, Qinying Li, Junrui Hu, Linjie Li, Yusen Xu, Xuejia Zhai, and Yongning Lu have no relevant conflicts of interest to declare.

Data availability

The data presented in this study are available from the corresponding author on reasonable request.

Ethical approval

The study was approved by the Medical Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology [approval no. (2022) 0945] on 10 January 2023. The study was performed in accordance with the Good Clinical Practice standards of China National Medical Products Administration, the current Declaration of Helsinki (as revised in 2013), and relevant regulations.

Consent to participate

Informed consent was obtained from all individual participants included in this study.

Author contributions

Conceptualization: All authors. Methodology: BD, QL, JH. Formal analysis and investigation: LL, YX. Writing – original draft preparation: YD. Writing – review and editing: LY, YW, YC, CL, XZ, YL. Funding acquisition: XZ, YL. Resources: LS, FX. Supervision: XZ, YL. Project administration: YL. All authors read and approved the final manuscript.

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Du, Y., Yu, L., Deng, B. et al. Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial. Clin Drug Investig (2024). https://doi.org/10.1007/s40261-024-01359-x

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