Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49-Box 921, 3000 Leuven, Belgium; Bayer AG, Research & Development, Pharmaceuticals, Model-Informed Drug Development, Building B106, 51368 Leverkusen, Germany.
Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49-Box 921, 3000 Leuven, Belgium.
Int J Pharm. 2024 Dec 5;666:124831. doi: 10.1016/j.ijpharm.2024.124831. Epub 2024 Oct 13.
Older adults are an inherently heterogeneous population with various underlying pathologies, medication use, and habits. In this study, the variability of this population was studied for the gastric and duodenal fluid volumes, as the amount of gastrointestinal volumes could play an essential role in the dissolution of drugs. The fluid volumes were retrospectively quantified by using magnetic resonance imaging (MRI). In 265 included fasted older individuals, the gastric fluid volume was 28.9 ± 21.1 mL (arithmetic mean ± standard deviation). No significant covariate-effect on stomach fluid volume was observed for various medication use, pathologies, and habits (e.g. hypertension, smoking, proton-pump inhibitors (PPIs), and aspirin). The gastric fluid volume remained constant with increasing age and had a high variability. The volumes and the variability were, however, not higher than the gastric values reported in healthy younger adults. The duodenal fluid volume was 16.6 ± 10.0 mL and a slight but statistically significant decrease with age was seen. In addition, cystic pancreas, obesity, diuretics, and PPI use demonstrated a moderate but significant correlation with the duodenal fluid volume. The findings of this study could be considered when developing and testing new drug candidates for the older adult population. For example, the volumes including their variability could be used as an input in physiologically based pharmacokinetic (PBPK) modelling approaches to predict drug exposure in this population.
老年人是一个具有固有异质性的人群，具有各种潜在的病理、用药和习惯。在这项研究中，研究了这个人群的胃和十二指肠液量的可变性，因为胃肠道量的多少可能在药物溶解中起重要作用。使用磁共振成像（MRI）对液体量进行了回顾性量化。在 265 名禁食的老年人中，胃内液量为 28.9±21.1ml（算术平均值±标准差）。各种药物使用、病理和习惯（如高血压、吸烟、质子泵抑制剂（PPIs）和阿司匹林）对胃内液量没有显著的协变量影响。胃内液量随年龄的增加而保持不变，且具有高度的可变性。然而，这些体积和可变性并不高于健康年轻成年人报告的胃内值。十二指肠液量为 16.6±10.0ml，且随年龄呈轻微但具有统计学意义的下降。此外，囊性胰腺、肥胖、利尿剂和 PPI 使用与十二指肠液量呈中度但显著相关。在为老年人群开发和测试新的候选药物时，可以考虑本研究的结果。例如，包括其可变性的体积可以用作生理基于药代动力学（PBPK）模型方法的输入，以预测该人群中的药物暴露。
