Night-time quiescence and morning activation in the human colon: effect on transit of dispersed and large single unit formulations.

Objectives 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. Methods 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. 111 In-labelled resin (150-300 μm) and a large 99m Tc-labelled non-disintegrating capsule (22 x 8 mm) were swallowed at either 0800h or 1700h. Main outcome measures The geometric centre of isotope (range 1-9) was calculated from serial scintiscans allowing comparison of overnight and daytime transit. Results 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. Conclusion 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.