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Radiographic Localization Study of a Novel Potassium-Competitive Acid Blocker, Vonoprazan, in the Rat Gastric Mucosa

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Abstract

Background

Vonoprazan fumarate (TAK-438) is a novel potassium-competitive acid blocker that appears to exert a longer/more potent antisecretory effect than lansoprazole due to high accumulation/slow clearance from the gastric glands. However, there is no direct evidence that vonoprazan selectively accumulates in gastric parietal cells of gastric glands.

Aim

To investigate the distribution of radioactivity in the rat stomach after single intravenous administration of [3H]-labeled vonoprazan.

Methods/results

Autoradioluminography of the stomach revealed that at 5 h after administration, radioactivity levels in the corpus mucosal layer was higher than radioactivity levels in the muscular layer, pylorus, and forestomach. At 24 h, although overall radioactivity was significantly decreased, the highest radioactivity was still observed in the mucosal layer. Accumulation of radioactivity in gastric parietal cells was quantitatively analyzed using microautoradiography. The number of silver granules in parietal cells from vonoprazan-injected rats was higher than in cells from a saline-injected rat. At 24 h, the number of granules was approximately at 20 % of the number of granules at 5 h. There was no clear deposition of granules in other components. At 5 h, radioactivity was measured at 1.799 µg Eq/g in the stomach and 0.172 µg Eq/mL in plasma. After 24 h, radioactivity had decreased to 0.584 µg Eq/g in the stomach and 0.078 µg Eq/mL in plasma.

Conclusions

Vonoprazan selectively accumulates in gastric parietal cells in the mucosal layer of the rat stomach after intravenous administration.

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Acknowledgments

Editorial assistance was provided by Luke Carey, PhD, of ProScribe—Envision Pharma Group, and was funded by Takeda Pharmaceutical Company Limited. ProScribe’s services complied with international guidelines for Good Publication Practice (GPP2). We thank Mr. Haruyuki Nishida (Pharmaceutical Research Division, Takeda pharmaceutical Company Limited) for his generous support in synthesizing [3H]-labeled vonoprazan. All experiments were conducted by Nemoto Science Co., Ltd, Ibaraki, Japan.

Funding

This study was funded by Takeda Pharmaceutical Company Limited.

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Authors and Affiliations

  1. Extra Value Generation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan

    Jun Matsukawa & Nobuhiro Inatomi

  2. DMPK Research Laboratory, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan

    Akifumi Kogame & Yoshihiko Tagawa

Authors
  1. Jun Matsukawa
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  2. Akifumi Kogame
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  3. Yoshihiko Tagawa
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  4. Nobuhiro Inatomi
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Corresponding author

Correspondence to Jun Matsukawa.

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Conflict of interest

All authors are employees of Takeda Pharmaceutical Company Limited.

Ethical standard

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

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Matsukawa, J., Kogame, A., Tagawa, Y. et al. Radiographic Localization Study of a Novel Potassium-Competitive Acid Blocker, Vonoprazan, in the Rat Gastric Mucosa. Dig Dis Sci 61, 1888–1894 (2016). https://doi.org/10.1007/s10620-016-4100-y

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  • DOI: https://doi.org/10.1007/s10620-016-4100-y

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