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基于机制的热量摄入对胃排空率和胆囊排空影响的建模

Mechanism-Based Modeling of Gastric Emptying Rate and Gallbladder Emptying in Response to Caloric Intake.

作者信息

Guiastrennec B, Sonne D P, Hansen M, Bagger J I, Lund A, Rehfeld J F, Alskär O, Karlsson M O, Vilsbøll T, Knop F K, Bergstrand M

机构信息

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

出版信息

CPT Pharmacometrics Syst Pharmacol. 2016 Dec;5(12):692-700. doi: 10.1002/psp4.12152.

Abstract

Bile acids released postprandially modify the rate and extent of absorption of lipophilic compounds. The present study aimed to predict gastric emptying (GE) rate and gallbladder emptying (GBE) patterns in response to caloric intake. A mechanism-based model for GE, cholecystokinin plasma concentrations, and GBE was developed on data from 33 patients with type 2 diabetes and 33 matched nondiabetic individuals who were administered various test drinks. A feedback action of the caloric content entering the proximal small intestine was identified for the rate of GE. The cholecystokinin concentrations were not predictive of GBE, and an alternative model linking the nutrients amount in the upper intestine to GBE was preferred. Relative to fats, the potency on GBE was 68% for proteins and 2.3% for carbohydrates. The model predictions were robust across a broad range of nutritional content and may potentially be used to predict postprandial changes in drug absorption.

摘要

餐后释放的胆汁酸会改变亲脂性化合物的吸收速率和程度。本研究旨在预测热量摄入后胃排空(GE)速率和胆囊排空(GBE)模式。基于33名2型糖尿病患者和33名匹配的非糖尿病个体的数据,建立了一个关于GE、胆囊收缩素血浆浓度和GBE的基于机制的模型,这些个体被给予了各种测试饮料。确定了进入近端小肠的热量含量对GE速率的反馈作用。胆囊收缩素浓度不能预测GBE,因此更倾向于选择一个将上肠道营养物质数量与GBE联系起来的替代模型。相对于脂肪,蛋白质对GBE的效力为68%,碳水化合物为2.3%。该模型预测在广泛的营养成分范围内都很稳健,并且可能潜在地用于预测餐后药物吸收的变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ea/5192972/79d45cc0cb77/PSP4-5-692-g001.jpg

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