Comparing the gastric emptying of 240 mL and 20 mL water by MRI and caffeine salivary tracer technique
Comparing the gastric emptying of 240 mL and 20 mL water by MRI and caffeine salivary tracer technique
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DOI：
10.1016/j.ejpb.2023.01.021
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发表时间：
2023-02-04
影响因子：
4.9
通讯作者：
Weitschies, Werner
中科院分区：
文献类型：
--
作者：
Grimm, Michael;Aude, Philipp;Weitschies, Werner
胃肠道液体体积是口服药物溶解和吸收的关键参数。临床标准设置中最常使用240 mL。尽管如此，对患者人群的调查显示，在真实的生活中口服药物的摄入量显著降低，甚至在一些临床研究中，液体体积减少也很常见。这些降低可能对药代动力学产生严重影响。因此，本研究的目的是比较8名健康志愿者240 mL和20 mL水的胃排空。为了研究胃液量，使用了具有强T2加权序列的磁共振成像。另外，通过在唾液中测量的咖啡因药代动力学来定量胃排空。摄入240 mL或20 mL后的绝对胃容量明显不同，相差10倍，但表示为每时间分数的相对胃排空几乎相当。仅观察到摄入20 mL后排空稍慢。唾液中咖啡因的药代动力学代表质量转移从胃到小肠摄入后的不同体积没有差异。在摄入240 mL后，吸收的咖啡因分数和排空的胃体积分数相关性良好，但在摄入20 mL后则不相关，表明摄入较小体积后分泌物对胃体积测量的影响更大。通过MRI和唾液咖啡因方法测量的相对胃排空仅略微延迟，因此，即使液体摄入量较低，经口给药的药物部分的转移也相当，这可以通过相当的咖啡因药代动力学看出。尽管如此，体积显著减少可能会干扰溶出和吸收。
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 in-fluence 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.