Vertzoni Maria, Koulouri Christina, Poulou Androniki, Goumas Konstantinos, Reppas Christos
Department of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
Department of Gastroenterology, Red Cross Hospital of Athens, Athens, Greece.
ADMET DMPK. 2020 Jun 15;8(2):122-128. doi: 10.5599/admet.846. eCollection 2020.
We explored the potential impact of Crohn's disease on the intragastric environment of fasted adults with a view to potential effects on intragastric performance of orally administered drugs in the fasted state. Data were collected from 15 healthy individuals and 15 patients with Crohn's disease. All subjects remained fasted for at least 12h prior to gastroscopy. Intragastric resting volume and pH were measured upon aspiration. Osmolality, surface tension, pepsin activity, and content of six bile acids were measured within 4 months upon sample collection. Unlike intragastric volumes, intragastric osmolality was significantly increased by Crohn's disease. However, mean osmolality value in patients was only slightly higher than in healthy individuals (293 vs. 257 mOsmol/kg, respectively), therefore, unlikely to affect intragastric drug product performance. Primarily due to the high variability of data in healthy individuals, the potential effects on intragastric pH and surface activity could not be evaluated on a statistical basis. However, based on average (mean and median) values, even if they are statistically significant, it seems unlikely to be of clinical significance. Inter-subject variability of pepsin activity, and total bile acids content was high in both the healthy and the patients' groups. Statistical investigation of the potential impact of Crohn's disease on these parameters requires prior designation of the minimum differences to be detected; such differences will determine the minimum sample size required of relevant investigations.
我们探讨了克罗恩病对空腹成年人胃内环境的潜在影响，目的是了解其对空腹状态下口服药物胃内性能的潜在作用。研究数据收集自15名健康个体和15名克罗恩病患者。所有受试者在胃镜检查前至少禁食12小时。通过抽吸测量胃内静息容积和pH值。在样本采集后的4个月内测量渗透压、表面张力、胃蛋白酶活性和六种胆汁酸的含量。与胃内容积不同，克罗恩病显著增加了胃内渗透压。然而，患者的平均渗透压值仅略高于健康个体（分别为293和257毫摩尔/千克），因此不太可能影响胃内药物产品的性能。主要由于健康个体数据的高度变异性，无法从统计学角度评估其对胃内pH值和表面活性的潜在影响。然而，基于平均值（均值和中位数），即使它们具有统计学意义，似乎也不太可能具有临床意义。健康组和患者组中胃蛋白酶活性和总胆汁酸含量的个体间变异性都很高。对克罗恩病对这些参数潜在影响的统计研究需要预先确定要检测的最小差异；这些差异将决定相关研究所需的最小样本量。
