School of Pharmacy, Institute of Clinical Sciences , University of Birmingham , Edgbaston , B15 2TT , U.K.
University Hospitals Coventry and Warwickshire NHS Trust , Clifford Bridge Road , Coventry CV2 2DX , U.K.
Mol Pharm. 2019 Sep 3;16(9):3896-3903. doi: 10.1021/acs.molpharmaceut.9b00510. Epub 2019 Aug 15.
The volume and localization of fluid in the paediatric gastrointestinal tract is crucial to the design of in vitro and in silico models that predict the absorption of oral drugs administered to children. Previous studies have used magnetic resonance imaging (MRI) to quantify fluid volumes and localization in the intestines of adults; this study is the first to undertake similar analysis of pediatric participants. This study quantified the amount and distribution of fluid in fasted and fluid-fed children using MRI data captured during the routine clinical assessment. Data from 32 fasted children (aged 0-16 years) and 23 fluid-fed children (aged 8-16 years) were evaluated. The gastric volume ranged from 0 to 9 mL in the fasted and 19-423 mL in the fluid-fed state. The small intestinal volume was recorded to be 0-51 mL in the fasted and 6-91 mL in the fluid-fed state with an average number of 7.7 and 22.4 fluid pockets, respectively. The data showed significant differences in gastric volumes and the number of fluid pockets in the small intestine for age-matched fasted and fluid-fed children ( < 0.05). Both the number and the volume of pockets reported in children are much lower than those previously reported in adults. This study is the first to report intestinal volumes and localization in children and provides new information to achieve the design of biorelevant in vitro models and real values to update in silico models. The data available from both fluid-fed and fasted children show the extremes of fluid volumes that are present in the gastro-intestinal tract which is useful to understand the variability associated with drug absorption in children.
小儿胃肠道内液体的容量和定位对于设计预测儿童口服药物吸收的体外和计算模型至关重要。先前的研究已经使用磁共振成像(MRI)来量化成人肠道内的液体量和定位;这项研究首次对儿科参与者进行了类似的分析。该研究使用 MRI 数据定量评估禁食和液体喂养儿童的液体量和分布,这些数据是在常规临床评估期间采集的。评估了 32 名禁食儿童(0-16 岁)和 23 名液体喂养儿童(8-16 岁)的数据。禁食状态下胃容量范围为 0-9 毫升,液体喂养状态下胃容量为 19-423 毫升。记录到的小肠容量在禁食状态下为 0-51 毫升,液体喂养状态下为 6-91 毫升,分别有平均 7.7 和 22.4 个液体袋。数据显示,年龄匹配的禁食和液体喂养儿童的胃容量和小肠内液体袋数量存在显著差异(<0.05)。与成人相比,儿童报告的液体袋数量和体积都要小得多。这项研究首次报告了儿童的肠道容量和定位,并提供了新的信息,以实现生物相关体外模型的设计和真实值更新计算模型。来自液体喂养和禁食儿童的数据均显示了胃肠道内存在的液体量的极值,这有助于了解与儿童药物吸收相关的变异性。