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

Objectives Controlling the delivery of drugs to different regions of the co lon remains an elusive goal. The aim of this study was to define the diurna l variation in colonic transit and show how this influences the colonic dis tribution and residence time of different formulations given either in the morning or evening, Methods Colonic transit of small particulates and a large capsule was measu red during nocturnal sleep and daytime wakefulness. Eighteen healthy volunt eers participated in a randomised crossover study. In-111-labelled resin (1 50-300 mu m) and a large Tc-99m-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 calcul ated from serial scintiscans allowing comparison of overnight and daytime t ransit. 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 im mediately after awakening, prior to breakfast, in 9/18 studies (P< 0.05), T he capsule was more distal than the resin at the end of the study 15 h afte r dosing (P< 0.001), There was marked inter-individual variability in distr ibution 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 th an dispersed small particles. However, substantial inter-individual variabi lity in transit makes targeting specific regions of the human colon unrelia ble with either dispersed or single unit formulations. fur J Gastroenterol Hepatol 11:1379-1385 (C) 1999 Lippincott Williams & Wilkins.