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Influence of daily versus alternate-day dosing of vonoprazan on intragastric pH, serum gastrin, and the antiplatelet function of clopidogrel

Influence of alternate-day dosing of vonoprazan

  • Pharmacodynamics
  • Published:
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Abstract

Background

Vonoprazan, a potassium-competitive acid blocker, inhibits gastric acid secretion and attenuates the antiplatelet function of clopidogrel more potently than esomeprazole. We investigated whether alternate-day dosing of vonoprazan might avoid this interaction with clopidogrel while providing sufficient gastric acid inhibition.

Methods

Following 24 h of pH monitoring (control regimen), 12 healthy volunteers received three regimens (clopidogrel-only regimen: clopidogrel 75 mg daily [q.d.]; vonoprazan alternate-day regimen: vonoprazan 10 mg every other day [q.o.d.] + clopidogrel 75 mg q.d.; vonoprazan daily regimen: vonoprazan 10 mg q.d. + clopidogrel 75 mg q.d.) for 14 days in a randomized open-label crossover manner. Intragastric pH monitoring was performed for 24 h on day 13 in the clopidogrel-only and vonoprazan q.d. regimens and for 48 h on days 13 and 14 in the vonoprazan q.o.d. regimen. Serum gastrin and inhibition of platelet aggregation (IPA) were measured before the commencement of pH monitoring in each regimen.

Results

Twelve volunteers completed the study. Equivalent median IPA values in the q.o.d. and q.d. regimens were measured (21.8% and 25%, respectively) and were significantly lower than that with the clopidogrel-only regimen (40.8%). The median pH4 holding time ratio for the vonoprazan q.o.d. regimen (49.7%) was superior to that of the clopidogrel-only regimen (18.4%), but was significantly inferior to that of the vonoprazan q.d. regimen (77.0%; p < 0.01).

Conclusion

Alternate-day administration of vonoprazan could not prevent the interaction between vonoprazan and clopidogrel, and acid inhibition was inferior to that with vonoprazan daily administration. Alternate-day administration of vonoprazan thus appears to be of questionable clinical utility.

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Abbreviations

VPZ:

Vonoprazan

CLP:

Clopidogrel

IPA:

The inhibition of ADP-induced platelet aggregation

pH4 HTR:

PH4 holding time ratio

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Acknowledgements

This work was performed by self-funding. We greatly appreciate Ms. Midori Ito and Ms. Emiko Otobe in the clinical research support section of Hamamatsu University School of Medicine for their monitoring of our study.

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Authors and Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Tomohiro Higuchi, Mihoko Yamade, Satoru Takahashi, Satoshi Tamura, Shinya Tani, Yasushi Hamaya & Ken Sugimoto

  2. Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Satoshi Tamura & Satoshi Osawa

  3. Department of Clinical Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Moriya Iwaizumi

  4. Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Takahisa Furuta

  5. Department of Gastroenterology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan

    Takuma Kagami

  6. Department of Gastroenterology, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan

    Takahiro Uotani

Authors
  1. Tomohiro Higuchi
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  2. Mihoko Yamade
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Contributions

Tomohiro Higuchi: Acquisition of pH monitoring data, help with statistical analysis and interpretation of data, drafting of the manuscript. Mihoko Yamade: Acquisition of pH monitoring data. Satoru Takahashi: Acquisition of pH monitoring data. Satoshi Tamura: Measurement of platelet coagulability by VerifyNow. Shinya Tani: Acquisition of pH monitoring data. Takuma Kagami: Acquisition of pH monitoring data. Takahiro Uotani: Acquisition of pH monitoring data. Yasushi Hamaya: Acquisition of pH monitoring data. Moriya Iwaizumi: Acquisition of pH monitoring data. Satoshi Osawa: Acquisition of pH monitoring data. Ken Sugimoto: Acquisition of pH monitoring data. Takahisa Furuta: Study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to Takahisa Furuta.

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Higuchi, T., Yamade, M., Takahashi, S. et al. Influence of daily versus alternate-day dosing of vonoprazan on intragastric pH, serum gastrin, and the antiplatelet function of clopidogrel. Eur J Clin Pharmacol 78, 955–963 (2022). https://doi.org/10.1007/s00228-022-03313-2

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