谷世寅, 仲云熙, 彭英, 金孝亮, 常青青, 王广基, 孙建国. 沃诺拉赞在急性肝损伤模型大鼠与正常大鼠体内药代动力学比较研究J. 药学学报, 2017,52(8): 1276-1281. doi: 10.16438/j.0513-4870.2017-0145
引用本文: 谷世寅, 仲云熙, 彭英, 金孝亮, 常青青, 王广基, 孙建国. 沃诺拉赞在急性肝损伤模型大鼠与正常大鼠体内药代动力学比较研究J. 药学学报, 2017,52(8): 1276-1281. doi: 10.16438/j.0513-4870.2017-0145
GU Shi-yin, ZHONG Yun-xi, PENG Ying, JIN Xiao-liang, CHANG Qing-qing, WANG Guang-ji, SUN Jian-guo. Comparative pharmacokinetic study of vonoprazan in acute hepatic injury rats and normal ratsJ. Acta Pharmaceutica Sinica, 2017,52(8): 1276-1281. doi: 10.16438/j.0513-4870.2017-0145
Citation: GU Shi-yin, ZHONG Yun-xi, PENG Ying, JIN Xiao-liang, CHANG Qing-qing, WANG Guang-ji, SUN Jian-guo. Comparative pharmacokinetic study of vonoprazan in acute hepatic injury rats and normal ratsJ. Acta Pharmaceutica Sinica, 2017,52(8): 1276-1281. doi: 10.16438/j.0513-4870.2017-0145

沃诺拉赞在急性肝损伤模型大鼠与正常大鼠体内药代动力学比较研究

Comparative pharmacokinetic study of vonoprazan in acute hepatic injury rats and normal rats

  • 摘要: 肝脏疾病目前已成为我国高发性疾病之一,胃肠道出血是肝脏疾病常见的并发症之一,现临床常用质子泵抑制剂类药物进行治疗。沃诺拉赞作为一种新型的质子泵抑制剂,可能可以替代目前常用的兰索拉唑作为临床有效抑制胃酸的药物。本实验主要探索并研究了沃诺拉赞在四氯化碳诱导的急性肝损伤大鼠血浆中的经时过程及其主要代谢物的生成情况。结果表明,在急性肝损伤大鼠体内,沃诺拉赞暴露量显著高于正常大鼠,代谢物生成速率降低,这可能是由于肝损伤影响了酶活性及转运体活性导致的。本研究为今后临床对肝脏疾病患者的用药调整提供了一定的理论依据。

     

    Abstract: Hepatic disease is one of the high-prevalence diseases in China, of which gastrointestinal bleeding is a common complication treated by proton pump inhibitors. Vonoprazan is a novel proton pump inhibitor which acts better than lansoprazole in pharmacokinetics and pharmacodynamics. In this study, the pharmacokinetics of vonoprazan was compared between acute hepatic injury and normal condition in rats. Results showed that the exposure (AUC) of vonoprazan was significantly higher in rats with acute hepatic injury than in normal rats, and the metabolites formation rates of vonoprazan also slowed down, which might be due to the change of activity of enzymes and transporters. This find may provide a theoretical basis for the dose regulation of vonoprazan in patients with hepatic injury.

     

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