Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability
Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability
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DOI：
10.1063/5.0096877
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发表时间：
2022-08-01
影响因子：
4.6
通讯作者：
Mittal, R.
中科院分区：
文献类型：
--
作者：
Lee, J. H.;Kuhar, S.;Mittal, R.
口服给药途径具有方便、成本低、患者依从性高等优点，是最常见的给药选择，口服药物的研发需求和投入持续增长。溶解的有效药物成分(API)进入十二指肠的溶出度和胃排空速度受胃动力、药丸的物理性质和胃内容物的调节，但目前用于评估口服药物体外溶出度的方法在概括这一过程方面存在局限性。这与胃轻瘫等改变胃解剖和/或生理的疾病状况特别相关。在电子计算机中，胃生物力学模型为克服现有方法的这些局限性提供了可能性。在本研究中，我们使用了一个基于胃的真实解剖和形态的仿生电子计算机模拟器(简称StomachSim)来研究和量化身体姿势和胃运动对药物生物利用度的影响。模拟表明，体位的改变可能会对API进入十二指肠的排空率产生显著(高达83%)的影响。同样，与胃轻瘫相关的胃窦收缩能力的降低也可以显著减少药丸的溶解和API进入十二指肠的排空。模拟表明，对于同等的运动指数，神经性胃轻瘫引起的胃排空减少比肌病胃轻瘫大约五倍。由AIP出版公司独家授权出版。
The oral route is the most common choice for drug administration because of several advantages, such as convenience, low cost, and high patient compliance, and the demand and investment in research and development for oral drugs continue to grow. The rate of dissolution and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum is modulated by gastric motility, physical properties of the pill, and the contents of the stomach, but current in vitro procedures for assessing dissolution of oral drugs 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 silico models of gastric biomechanics offer the potential for overcoming these limitations of existing methods. In the current study, we employ a biomimetic in silico simulator based on the realistic anatomy and morphology of the stomach (referred to as StomachSim) to investigate and quantify the effect of body posture and stomach motility on drug bioavailability. The simulations show that changes in posture can potentially have a significant (up to 83%) effect on the emptying rate of the API into the duodenum. Similarly, a reduction in antral contractility associated with gastroparesis can also be found to 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, the reduction in gastric emptying due to neuropathic gastroparesis is larger by a factor of about five compared to myopathic gastroparesis. Published under an exclusive license by AIP Publishing.