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Dig Dis Sci. 2016 Jul;61(7):1888-94. doi: 10.1007/s10620-016-4100-y. Epub 2016 Mar 9.

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

Author information

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@takeda.com.
2
DMPK Research Laboratory, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.
3
Extra Value Generation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.

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 [(3)H]-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.

KEYWORDS:

Gastric mucosa; Gastroesophageal reflux disease; Potassium-competitive acid blocker; Rat; TAK-438; Vonoprazan

Comment in

PMID:
26961787
DOI:
10.1007/s10620-016-4100-y
[Indexed for MEDLINE]

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