Department of Biopharmaceutics and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Felix-Hausdorff-Straße 3, 17489 Greifswald, Germany.
Department of Clinical Pharmacology, Bayer AG Pharmaceuticals, 13353 Berlin, Germany.
Eur J Pharm Biopharm. 2023 Mar;184:150-158. doi: 10.1016/j.ejpb.2023.01.021. Epub 2023 Feb 1.
Gastrointestinal fluid volumes are a crucial parameter for dissolution and absorption of orally taken medications. Most often 240 mL are used in clinical standard setups. Nonetheless, surveys in patient populations revealed dramatically lower volumes for intake of oral medications in real life and even in some clinical studies reduced fluid volumes are common. These reductions might have serious impact on pharmacokinetics. Thus, it was the aim of this study to compare the gastric emptying of 240 mL and 20 mL of water in 8 healthy volunteers. For investigation of gastric fluid volumes Magnetic Resonance Imaging with strongly T2 weighted sequences was used. Gastric emptying was additionally quantified via caffeine pharmacokinetics measured in saliva. The absolute gastric volumes after intake of 240 mL or 20 mL obviously differed by factor 10 but relative gastric emptying expressed as fraction per time was nearly comparable. Only slighter slower emptying after intake of 20 mL was observed. Salivary caffeine pharmacokinetics representing mass transfer from stomach to small intestine after intake of different volumes did not differ. The absorbed caffeine fraction and emptied gastric volume fraction correlated well after intake of 240 mL, but not after intake of 20 mL, indicating a higher influence of secretion on gastric volume measurements after intake of smaller volumes. Relative gastric emptying as measured with MRI and salivary caffeine method was only slightly delayed, thus transfer of orally administered drug fraction could be comparable even with lower fluid intake as can be seen by comparable caffeine pharmacokinetics. Nonetheless, the considerably reduced volumes might interfere with dissolution and absorption.
胃肠道液量是溶解和吸收口服药物的一个关键参数。在临床标准设置中，最常用的是 240 毫升。然而，在患者人群中的调查显示，实际生活中口服药物的摄入量要低得多，甚至在一些临床研究中，减少液体量也很常见。这些减少可能对药代动力学有严重影响。因此，本研究的目的是比较 8 名健康志愿者分别饮用 240 毫升和 20 毫升水的胃排空情况。为了研究胃内液量，使用了具有强烈 T2 加权序列的磁共振成像。通过测量唾液中的咖啡因药代动力学，进一步定量胃排空。饮用 240 毫升或 20 毫升后，绝对胃容量明显相差 10 倍，但相对胃排空（表示为每时间的分数）几乎相当。仅观察到饮用 20 毫升后排空稍慢。代表不同体积摄入后从胃到小肠的质量转移的唾液咖啡因药代动力学无差异。在摄入 240 毫升后，吸收的咖啡因分数和排空的胃容量分数相关性良好，但在摄入 20 毫升后则没有，这表明在摄入较小体积后，分泌对胃容量测量的影响更大。用 MRI 和唾液咖啡因法测量的相对胃排空仅略有延迟，因此即使液体摄入量较低，口服给予的药物分数也可能相似，这可以从相似的咖啡因药代动力学中看出。然而，大量减少可能会干扰溶解和吸收。
