Hebden J M, Gilchrist P J, Blackshaw E, Frier M E, Perkins A C, Wilson C G, Spiller R C
Division of Gastroenterology, University of Nottingham, UK.
Eur J Gastroenterol Hepatol. 1999 Dec;11(12):1379-85. doi: 10.1097/00042737-199912000-00007.
Controlling the delivery of drugs to different regions of the colon remains an elusive goal. The aim of this study was to define the diurnal variation in colonic transit and show how this influences the colonic distribution and residence time of different formulations given either in the morning or evening.
Colonic transit of small particulates and a large capsule was measured during nocturnal sleep and daytime wakefulness. Eighteen healthy volunteers participated in a randomised crossover study. 111In-labelled resin (150-300 microm) and a large 99mTc-labelled non-disintegrating capsule (22 x 8 mm) were swallowed at either 0800h or 1700h.
The geometric centre of isotope (range 1-9) was calculated from serial scintiscans allowing comparison of overnight and daytime transit.
Transit of resin was delayed in the overnight compared to daytime 8 h periods (change in geometric centres (GCs), mean +/- SEM, 0.59 +/- 0.14 vs 1.46 +/- 0.39 respectively, P < 0.02). Maximal resin movement occurred immediately after awakening, prior to breakfast, in 9/18 studies (P < 0.05). The capsule was more distal than the resin at the end of the study 15 h after dosing (P < 0.001). There was marked inter-individual variability in distribution of both resin and capsule at 15 h, the range of GCs being 2.8-9 and 2.2-9, respectively.
Sleep delays colonic transit and large capsules travel faster than dispersed small particles. However, substantial inter-individual variability in transit makes targeting specific regions of the human colon unreliable with either dispersed or single unit formulations.
控制药物向结肠不同区域的递送仍然是一个难以实现的目标。本研究的目的是确定结肠转运的昼夜变化，并展示其如何影响早晨或晚上给予的不同制剂在结肠中的分布和停留时间。
在夜间睡眠和白天清醒期间测量小颗粒和大胶囊的结肠转运。18名健康志愿者参与了一项随机交叉研究。在08:00或17:00吞咽111In标记的树脂（150 - 300微米）和一个大的99mTc标记的不崩解胶囊（22×8毫米）。
根据系列闪烁扫描计算同位素的几何中心（范围1 - 9），以便比较夜间和白天的转运情况。
与白天8小时时间段相比，夜间树脂的转运延迟（几何中心（GCs）变化，平均值±标准误，分别为0.59±0.14和1.46±0.39，P < 0.02）。在9/18项研究中，最大树脂移动发生在醒来后、早餐前（P < 0.05）。给药15小时后研究结束时，胶囊比树脂更靠近远端（P < 0.001）。在15小时时，树脂和胶囊的分布存在明显的个体间差异，GCs范围分别为2.8 - 9和2.2 - 9。
睡眠会延迟结肠转运，大胶囊比分散的小颗粒移动得更快。然而，转运过程中存在的个体间差异使得无论是分散制剂还是单一单元制剂，靶向人类结肠的特定区域都不可靠。
