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Pharmacokinetic Interaction of Anaprazole, Amoxicillin and Clarithromycin after Single-Dose Simultaneous Administration and the Effect of Adding Bismuth on Their Pharmacokinetics in Healthy Male Chinese Subjects

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Abstract

Background and Objective

Helicobacter pylori-positive ulcers are treated with a proton pump inhibitor (PPI) + two antibiotics with/without bismuth. The objective of this study was to investigate the pharmacokinetic interaction of the novel PPI anaprazole, amoxicillin and clarithromycin with/without bismuth.

Methods

This single-centre, randomised, open-label phase 1 pharmacokinetic study included healthy Chinese male participants, comprising two cohorts (cohort 1, 4 × 4 crossover design; cohort 2, 2 × 2 crossover design). In cohort 1, 24 participants received four treatment cycles with a different treatment in each cycle; the washout period between cycles was 9 days. Participants were randomly assigned to one of the following four treatment sequences (1:1:1:1): anaprazole sodium enteric-coated tablet 20 mg monotherapy, amoxicillin 1000 mg monotherapy, clarithromycin 500 mg monotherapy, and a three-drug combination (anaprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg). During each treatment cycle, study drugs were administered twice daily for four consecutive days and once in the morning on the fifth day. Cohort 2 participants were administered a single dose of the three-drug combination and a single dose of a four-drug combination (three-drug combination + bismuth 0.6 g) with a washout period of 11 ± 2 days between treatments. Blood samples were collected for pharmacokinetic analysis.

Results

Twenty-nine of 32 enrolled participants (cohort 1, n = 24; cohort 2, n = 8) completed the study. There were no significant differences in exposure or time to reach maximum concentration (Tmax) between each single drug or the three-drug combination (cohort 1) or between the three- and four-drug combinations (cohort 1) for any of the drugs/metabolites.

Conclusions

Dose adjustments for individual drugs are not necessary with combined dosing of anaprazole, amoxicillin, clarithromycin and bismuth.

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Acknowledgements

The authors thank Sarah Bubeck, PhD, of Edanz (www.edanz.com) for providing medical writing support, which was funded by Xuanzhu (Beijing) Pharmaceutical Technology Co., Ltd., in accordance with Good Publication Practice (GPP 2022) guidelines (https://www.ismpp.org/gpp-2022).

Author information

Author notes

  1. Sijia Ding and Lijun Xie are co-first authors and contributed equally to this paper.

Authors and Affiliations

  1. Phase I Clinical Trial Unit, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

    Sijia Ding, Lijun Xie, Lu Wang, Chen Zhou, Sufeng Zhou, Juan Chen, Bei Zhu, Yun Liu & Feng Shao

  2. Xuanzhu Technology Co., Ltd., Shijiazhuang, 050000, China

    Li Wang & Zhen Zhang

  3. Department of Clinical Pharmacology, School of Pharmacy College, Nanjing Medical University, Nanjing, 211166, China

    Jinying Zhu, Zeru Zhang, Tongtong Li & Feng Shao

Authors
  1. Sijia Ding
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  2. Lijun Xie
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  3. Lu Wang
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  4. Chen Zhou
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  5. Sufeng Zhou
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  6. Juan Chen
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  7. Bei Zhu
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  8. Yun Liu
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  9. Jinying Zhu
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  11. Tongtong Li
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  12. Li Wang
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  14. Feng Shao
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Corresponding author

Correspondence to Feng Shao.

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Funding

This study was funded by Xuanzhu (Beijing) Pharmaceutical Technology Co., Ltd.

Conflict of interest

The authors have indicated that they have no conflicts of interest associated with the content of this article.

Ethics approval statement

This study was approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

All participants provided written informed consent.

Consent for publication

Not applicable.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

Author contributions

Substantial contributions to the conception and design of the work were made by F.S. Administrative support and provision of study materials or participants were carried out by S.D., L.X., C.Z., S.Z., Z.Y., J.C., B.Z., J.Z., T.L., and Zeru.Z. Substantial contributions to collection and assembly of data were made by S.D., L.X., and J.C. Substantial contributions to data analysis and interpretation were made by L.W. and F.S. Substantial contributions to manuscript writing were made by S.D., L.X., L.W., F.S., and Y.L. made substantial contributions to quality assurance of this clinical trial. Zhen.Z. substantially contributed to the clinical operation of this trial. Final approval of the manuscript was given by all the authors.

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Ding, S., Xie, L., Wang, L. et al. Pharmacokinetic Interaction of Anaprazole, Amoxicillin and Clarithromycin after Single-Dose Simultaneous Administration and the Effect of Adding Bismuth on Their Pharmacokinetics in Healthy Male Chinese Subjects. Eur J Drug Metab Pharmacokinet 48, 121–132 (2023). https://doi.org/10.1007/s13318-022-00810-8

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