偏好的美罗胺吸收被1α,25-二氧维生素D激活,并与酸盐输送基质斯卡内特共享,在老鼠皮质中
Toshihide Saito1, Yuichi Ichimura1, Masako Oda1
1Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari, Tobetsu, Hokkaido, 061-0293, Japan.
梅罗 (MEPM) 首选在老鼠大脑中被吸收,可能是通过与福斯卡内特共享的载体. 维生素D显著增强了MEPM的吸收,这表明了口服配方的新途径.
科学领域:
- 药物动力学和药物吸收 药物吸收
- 胃肠道生理学 胃肠道生理学
- 分子运输机制分子运输机制
背景情况:
- 梅罗 (MEPM) 是一种关键的卡巴胺抗生素,用于重症感染,目前只能以注射形式提供.
- 开发一种口服配方的MEPM将大大提高其临床实用性和患者的便利性.
- 了解MEPM的肠道吸收特性对于开发这种口服配方至关重要.
研究的目的:
- 为了研究Meropenem (MEPM) 在大鼠小肠中的吸收特性.
- 为了确定潜在的载体和参与MEPM肠道吸收的调节因素.
- 探索增强口服药物输送中MEPM吸收的可行性.
主要方法:
- 利用现场循环技术研究小鼠小肠不同部分的MEPM吸收.
- 采用了体外扩散室方法来评估M-to-S (从粘膜到血清) 透率.
- 研究了福斯卡内特,糖糖,胺,陶罗胆酸,双胺和1α,25-二氧维生素D3 (1,25(OH) 2D3对MEPM吸收和透的影响.
主要成果:
- 与十二指肠和十足肠相比,MEPM在大肠中显示出更高的消失比率.
- 福斯卡内特显著减少了MEPM在皮质体中的消失,这表明共享的运输机制.
- 1α,25-二氧维生素D3 (1,25(OH) 2D3) 显著增加了MEPM的M-to-S穿透度在脏中超过7倍.
结论:
- 梅罗 (MEPM) 首选吸收在老鼠皮质中,可能涉及Na+依赖酸盐输送体 (NaPi-T) 或相关的输送体.
- 皮膜中MEPM的吸收似乎由1α,25-二氧维生素D3 (1,25(OH) 2D3) 调节,这表明口服药物开发的潜在途径.
- 这些发现为开发美罗 (MEPM) 新型口服配方提供了基础.
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