Drug Delivery & Disposition, KU Leuven , Gasthuisberg O&N2, Herestraat 49 Box 921, 3000 Leuven, Belgium.
Pharmaceutical Analysis, KU Leuven , Gasthuisberg O&N2, Herestraat 49 Box 923, 3000 Leuven, Belgium.
Mol Pharm. 2017 Dec 4;14(12):4202-4208. doi: 10.1021/acs.molpharmaceut.7b00252. Epub 2017 Aug 11.
This study determined intraluminal ethanol concentrations (stomach and duodenum) in fed healthy volunteers after the consumption of common alcoholic beverages (beer, wine, and whisky). The results of this study were compared with a previous study in fasted volunteers. Five healthy volunteers were recruited in a crossover study. The fed state was simulated by ingestion of 250 mL of Nutridrink Compact Neutral. Volunteers subsequently consumed two standard units of beer (Stella Artois, 500 mL, 5.2% ethanol), wine (Blanc du Blanc, 200 mL, 11% ethanol), or whisky (Gallantry Whisky, 80 mL, 40% ethanol). Gastric and duodenal fluids were aspirated through two catheters over time and analyzed for ethanol content by head space gas chromatography. The capability of ethanol to permeate gastric and duodenal rat mucosa was examined in an Ussing chambers setup. A similar average gastric C was observed in the beer and the wine conditions: 3.3% and 3.7% ethanol, respectively. The gastric C in the whisky condition amounted to 8.5% ethanol. Lower ethanol concentrations were observed in the duodenum compared to the stomach. The duodenal C was similar in all three conditions: 1.3%, 1.2%, and 1.6% ethanol for beer, wine, and whisky, respectively. Compared to the fasted state (reported in a previous study), higher gastric ethanol concentrations were observed during a longer time period. In the beer and wine conditions, similar concentrations were observed in the intestine regardless of the prandial state. After intake of whisky, however, the ethanol concentration was lower in the fed intestine. Alcohol was observed to permeate both gastric and duodenal rat mucosa. Higher intragastric ethanol concentrations were maintained for a longer period of time in fed compared to fasted state conditions. However, the observed concentration profiles were not in line with current FDA guidelines for alcohol resistance testing of formulations, stating that in vitro tests should investigate the impact of up to 40% ethanol for 2 h. The presented intraluminal ethanol concentrations may serve as reference data for the further development of relevant in vitro models to assess ethanol effects on formulation performance.
本研究测定了进食健康志愿者在摄入常见酒精饮料(啤酒、葡萄酒和威士忌)后胃和十二指肠内的腔内乙醇浓度。将本研究的结果与之前在禁食志愿者中进行的研究进行了比较。在一项交叉研究中招募了 5 名健康志愿者。通过摄入 250 毫升 Nutridrink Compact Neutral 模拟进食状态。志愿者随后分别饮用 2 个标准单位的啤酒(Stella Artois,500 毫升,5.2%乙醇)、葡萄酒(Blanc du Blanc,200 毫升,11%乙醇)或威士忌(Gallantry Whisky,80 毫升,40%乙醇)。通过两个导管随时间抽吸胃和十二指肠液体,并通过顶空气相色谱法分析乙醇含量。在 Ussing 室装置中检查了乙醇渗透胃和十二指肠大鼠黏膜的能力。在啤酒和葡萄酒条件下观察到相似的平均胃 C:分别为 3.3%和 3.7%乙醇。在威士忌条件下胃 C 达到 8.5%乙醇。与胃相比,十二指肠中观察到的乙醇浓度较低。在所有三种条件下,十二指肠 C 相似:啤酒、葡萄酒和威士忌分别为 1.3%、1.2%和 1.6%乙醇。与空腹状态(在之前的研究中报道)相比,在较长时间内观察到较高的胃内乙醇浓度。在啤酒和葡萄酒条件下,无论进食状态如何,肠道中观察到的浓度相似。然而,在摄入威士忌后,进食肠道中的乙醇浓度较低。观察到酒精渗透胃和十二指肠大鼠黏膜。与禁食状态相比,进食状态下胃内更高的乙醇浓度保持更长时间。然而,观察到的浓度曲线与当前 FDA 关于制剂耐酒精性测试的指南不一致,该指南指出,体外测试应调查高达 40%乙醇的影响持续 2 小时。所呈现的腔内乙醇浓度可作为进一步开发相关体外模型的参考数据,以评估乙醇对制剂性能的影响。