Schulze Julia D R, Peters Erin E, Vickers Ann W, Staton J Scott, Coffin Mark D, Parsons Gary E, Basit Abdul W
Department of Pharmaceutics, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Int J Pharm. 2005 Aug 26;300(1-2):67-75. doi: 10.1016/j.ijpharm.2005.05.004.
Previous work has shown that polyethylene glycol 400 (PEG 400) has an accelerating effect on gastrointestinal transit and a modulating influence on drug absorption in humans. The aim of this study was to assess the impact of various excipients, PEG 400, propylene glycol, d-alpha-tocopheryl-polyethylene glycol-1000 succinate (TPGS) and Labrasol on gastrointestinal transit and drug absorption in four beagle dogs using scintigraphy. Each dog received, on five separate occasions, water (control) or a dose of excipient equivalent to 1 g PEG 400, 2 g propylene glycol, 1 g TPGS or 2 g Labrasol dissolved in water and administered in the form of two capsules. The model drugs ampicillin (200mg) and antipyrine (100mg) were co-administered in the capsules. The capsule solutions were radiolabelled with technetium-99m to follow their transit using a dual-headed gamma camera, and blood samples were collected to determine drug pharmacokinetics. On a separate occasion, the drugs were dissolved in saline and given intravenously. The capsules rapidly disintegrated in the stomach liberating their liquid contents. The mean small intestinal transit times for the different treatments (control, PEG 400, propylene glycol, TPGS and Labarasol) were 183, 179, 195, 168 and 154 min, respectively. The corresponding mean absolute oral bioavailability figures were 36, 32, 39, 42 and 32% for ampicillin and 76, 74, 85, 73 and 74% for antipyrine, respectively. The transit and bioavailability data for the excipient treatments were not significantly different from the control. In summary, these excipients, at the doses administered, have limited influence on gastrointestinal transit and drug in beagle dogs.
先前的研究表明，聚乙二醇400（PEG 400）对人体胃肠道转运具有加速作用，并对药物吸收有调节影响。本研究的目的是使用闪烁扫描法评估四种比格犬中各种辅料（PEG 400、丙二醇、d-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）和Labrasol）对胃肠道转运和药物吸收的影响。每只狗在五个不同的场合分别接受水（对照）或相当于1 g PEG 400、2 g丙二醇、1 g TPGS或2 g Labrasol的辅料剂量，将其溶解于水中并制成两个胶囊给药。模型药物氨苄西林（200mg）和安替比林（100mg）与辅料共同装入胶囊中。胶囊溶液用99m锝进行放射性标记，使用双头γ相机追踪其转运过程，并采集血样以确定药物的药代动力学。在另一个场合，将药物溶解于盐水中并静脉注射。胶囊在胃中迅速崩解，释放出其液体内容物。不同处理（对照、PEG 400、丙二醇、TPGS和Labrasol）的平均小肠转运时间分别为183、179、195、168和154分钟。氨苄西林相应的平均绝对口服生物利用度分别为36%、32%、39%、42%和32%，安替比林分别为76%、74%、85%、73%和74%。辅料处理的转运和生物利用度数据与对照无显著差异。总之，在所用剂量下，这些辅料对比格犬的胃肠道转运和药物影响有限。
