Radiographic Localization Study of a Novel Potassium-Competitive Acid Blocker, Vonoprazan, in the Rat Gastric Mucosa
Radiographic Localization Study of a Novel Potassium-Competitive Acid Blocker, Vonoprazan, in the Rat Gastric Mucosa
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DOI：
10.1007/s10620-016-4100-y
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发表时间：
2016-07-01
影响因子：
3.1
通讯作者：
Inatomi, Nobuhiro
中科院分区：
文献类型：
--
作者：
Matsukawa, Jun;Kogame, Akifumi;Inatomi, Nobuhiro
富马酸沃诺拉赞（TAK-438）是一种新型钾竞争性酸阻滞剂，由于其在胃腺中的高蓄积/缓慢清除，其抗分泌作用似乎比兰索拉唑更持久/更强效。然而，没有直接证据表明沃诺拉赞选择性地蓄积在胃腺的胃壁细胞中。为了研究[H-3]标记的沃诺拉赞单次静脉给药后大鼠胃中的放射性分布，胃放射自显影显示，给药后5 h，胃体粘膜层中的放射性水平高于肌层、幽门、和前胃在24 h时，尽管总体放射性显著降低，但在粘膜层中仍观察到最高放射性。使用显微放射自显影术定量分析胃壁细胞中的放射性蓄积。沃诺拉赞注射大鼠壁细胞中的银颗粒数量高于生理盐水注射大鼠的细胞。在24 h时，颗粒数量约为5 h时颗粒数量的20%。其他组分中无明显颗粒沉积。在5 h时，胃中的放射性测定值为1.799 A μ g Eq/g，血浆中的放射性测定值为0.172 A μ g Eq/mL。24 h后，胃中的放射性降低至0.584 A μ g Eq/g，血浆中的放射性降低至0.078 A μ g Eq/mL。静脉给药后，沃诺拉赞选择性蓄积在大鼠胃粘膜层的胃壁细胞中。
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.To investigate the distribution of radioactivity in the rat stomach after single intravenous administration of [H-3]-labeled vonoprazan.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 A mu g Eq/g in the stomach and 0.172 A mu g Eq/mL in plasma. After 24 h, radioactivity had decreased to 0.584 A mu g Eq/g in the stomach and 0.078 A mu g Eq/mL in plasma.Vonoprazan selectively accumulates in gastric parietal cells in the mucosal layer of the rat stomach after intravenous administration.