论文标题

胃中药物溶解的计算模型:姿势和胃轻瘫对药物生物利用度的影响

Computational model of drug dissolution in the stomach: effects of posture and gastroparesis on drug bioavailability

论文作者

Lee, Jae H., Kuhar, Sharun, Seo, Jung-Hee, Pasricha, Pankaj J., Mittal, Rajat

论文摘要

由于方便,低成本和高病人的依从性,口头途径是药物管理的最常见选择,但也是一条复杂的途径。溶解活性药物成分(API)溶解和胃排空的速率受到胃运动等因素的调节,但是当前评估药物溶解的电磁体程序的限制是限制其概括此过程的能力。这与改变胃的解剖结构和/或生理学等疾病疾病尤其重要。在这项研究中,我们基于胃部的解剖结构和胃形态采用了仿生内模拟器,以研究身体姿势和胃运动对药物生物利用度的影响。模拟表明,姿势的变化可能会对API的排空速率产生显着影响(高达83%)。同样,与胃轻瘫相关的肛门收缩力的降低也可以显着减少药丸的溶解以及将API排入十二指肠。该模拟表明,对于等效的运动指数,与肌性胃肉食相比,由于神经性胃轻瘫而导致的胃排空减少约为五倍。

The oral route is the most common choice for drug administration because of convenience, low cost, and high patient compliance, but is also a complex route. The rate of dissolution and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum is modulated by factors such as gastric motility, but current in-vitro procedures for assessing drug dissolution are limited in their ability to recapitulate this process. This is particularly relevant for disease conditions, such as gastroparesis, that alter the anatomy and/or physiology of the stomach. In this study we employ a biomimetic in-silico simulator based on the realistic anatomy and morphology of the stomach, to investigate the effect of body posture and stomach motility on drug bioavailability. The simulations show that changes in posture can have a significant (up to 83%) effect on the emptying rate of the API into the duodenum. Similarly, reduction in antral contractility associated with gastroparesis can also significantly reduce the dissolution of the pill as well as emptying of the API into the duodenum. The simulations show that for an equivalent motility index, reduction in gastric emptying due to neuropathic gastroparesis is larger by a factor of about five compared to myopathic gastroparesis.

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