Koziolek Mirko, Grimm Michael, Garbacz Grzegorz, Kühn Jens-Peter, Weitschies Werner
Institute of Pharmacy, Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Ernst Moritz Arndt University of Greifswald , Felix-Hausdorff-Straße 3, D-17487 Greifswald, Germany.
Mol Pharm. 2014 May 5;11(5):1632-9. doi: 10.1021/mp500022u. Epub 2014 Apr 15.
The aim of this magnetic resonance imaging (MRI) study was to investigate gastric emptying after intake of a high-caloric and high-fat standard meal as recommended by FDA and EMA for food-effect bioavailability and fed bioequivalence studies. Twelve healthy human subjects (7 male, 5 female) received the standard meal after an overnight fast. MRI was performed before as well as 15, 25, 35, 45, 55, 65, 105, 195, 275, and 375 min after meal intake using strong T2-weighted sequences and chemical shift imaging. In addition, 30 min after the beginning of meal intake subjects ingested 240 mL of water representing the recommended coadministration of water during drug intake. Gastric content volume was assessed using T2-weighted images, and fat fraction was estimated using a calculation of fat fraction in chemical shift imaging. In addition, the existence of a mechanism allowing fast gastric emptying of water in the fed state was investigated. After a lag phase of 50-90 min, gastric content volume decreased constantly with a rate of 1.7 mL/min. The water ingested 30 min after the start of the meal intake directly reached the antrum and subsequently was emptied quickly from the human stomach. Complete gastric emptying within 6 h was observed in only one out of 12 subjects. The fat fraction of the intragastric chyme decreased from 9.5% directly after meal intake to 6.3% at the end of the experiments. Moreover, the fat fraction in fundus was significantly higher compared to the antrum. This study contributes fundamental data for the assessment of food effects of solid oral dosage forms.
本磁共振成像（MRI）研究的目的是，按照美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）对食物效应生物利用度和进食状态生物等效性研究的建议，探究摄入高热量高脂肪标准餐后的胃排空情况。12名健康受试者（7名男性，5名女性）在禁食过夜后进食标准餐。在进食前以及进食后15、25、35、45、55、65、105、195、275和375分钟，使用强T2加权序列和化学位移成像进行MRI检查。此外，在进食开始后30分钟，受试者摄入240毫升水，这代表了药物摄入期间推荐的水的共同给药量。使用T2加权图像评估胃内容物体积，并通过化学位移成像中的脂肪分数计算来估计脂肪分数。此外，还研究了在进食状态下允许水快速胃排空的机制的存在情况。在50 - 90分钟的延迟期后，胃内容物体积以1.7毫升/分钟的速度持续下降。进食开始后30分钟摄入的水直接到达胃窦，随后迅速从人体胃中排空。12名受试者中只有1人在6小时内完全胃排空。胃内食糜的脂肪分数从进食后立即的9.5%降至实验结束时的6.3%。此外，胃底的脂肪分数明显高于胃窦。本研究为评估固体口服剂型的食物效应提供了基础数据。
