Kenyon C J, Nardi R V, Wong D, Hooper G, Wilding I R, Friend D R
Pharmaceutical Profiles Ltd, Highfields Science Park, Nottingham, UK.
Aliment Pharmacol Ther. 1997 Feb;11(1):205-13. doi: 10.1046/j.1365-2036.1997.93265000.x.
Colonic delivery of corticosteroids may reduce the side-effects commonly associated with their use. Therefore, we tested the ability of the naturally occurring polysaccharide guar gum to deliver a corticosteroid, dexamethasone, to the colon using pharmacoscintigraphy. Guar gum is metabolized in the colon by resident bacterial enzymes to trigger drug release.
Each subject (eight per group, parallel study design) was administered one of four dexamethasone (9 mg) tablet formulations, radiolabelled with 153Sm using neutron activation, under fasted conditions. One formulation was designed to release drug rapidly following ingestion while the other three formulations were designed to delay release of dexamethasone to varying degrees. Progression of the formulations down the gastrointestinal tract was followed by gamma scintigraphy. Serum concentrations were measured over time to relate disintegration profiles of the tablets with pharmacokinetic observations.
The immediate release formulation disintegrated in the stomach, on average, within 20 min of dosing. One of the three delayed release preparations (CD1) began to disintegrate in the small intestine 1.7 +/- 1.0 h after dosing. The second and third delayed release preparations (CD2 and CD3) did not begin to disintegrate until 5.8 +/- 2.3 and 3.6 +/- 1.6 h after dosing, respectively. All three colonic delivery preparations completely disintegrated in the colon ranging from 7.8 +/- 2.7 h (CD1) to 12.4 +/- 3.2 h (CD2) following oral administration. Pharmacoscintigraphic data indicated that 72-82% of the dexamethasone was delivered into the colon although not all the dexamethasone delivered into the colon was absorbed.
Simple guar gum formulations are capable of delivering the corticosteroid dexamethasone to the colon of normal subjects. Locally delivered corticosteroids may be useful in the treatment of ulcerative colitis and Crohn's disease. Pharmacoscintigraphic evaluation is a useful method to discriminate between the in vivo behaviour of colonic delivery systems.
结肠给药皮质类固醇可能会减少其使用中常见的副作用。因此，我们使用药物闪烁扫描法测试了天然存在的多糖瓜尔胶将皮质类固醇地塞米松递送至结肠的能力。瓜尔胶在结肠中被常驻细菌酶代谢以触发药物释放。
在禁食条件下，每组八名受试者（平行研究设计）服用四种用中子活化法用153Sm进行放射性标记的地塞米松（9毫克）片剂制剂中的一种。一种制剂设计为在摄入后迅速释放药物，而其他三种制剂设计为在不同程度上延迟地塞米松的释放。通过γ闪烁扫描法追踪制剂在胃肠道中的推进情况。随时间测量血清浓度，以将片剂的崩解情况与药代动力学观察结果相关联。
速释制剂在给药后平均20分钟内在胃中崩解。三种缓释制剂之一（CD1）在给药后1.7±1.0小时开始在小肠中崩解。第二种和第三种缓释制剂（CD2和CD3）分别直到给药后5.8±2.3小时和3.6±1.6小时才开始崩解。口服给药后，所有三种结肠给药制剂在结肠中完全崩解，时间范围从7.8±2.7小时（CD1）到12.4±3.2小时（CD2）。药物闪烁扫描数据表明，72 - 82%的地塞米松被递送至结肠，尽管并非所有递送至结肠的地塞米松都被吸收。
简单的瓜尔胶制剂能够将皮质类固醇地塞米松递送至正常受试者的结肠。局部递送皮质类固醇可能对溃疡性结肠炎和克罗恩病的治疗有用。药物闪烁扫描评估是区分结肠给药系统体内行为的有用方法。
