Limited exposure of the healthy distal colon to orally-dosed formulation is further exaggerated in active left-sided ulcerative colitis

Background: Active distal ulcerative colitis is often resistant to topicall y acting oral formulations. We speculated that the left side of the colon i s underexposed to orally-dosed topical agents in patients with active dista l colitis. Methods: Twenty-two healthy volunteers (12 males, aged 22-47 years), and 10 patients (6 males, aged 33-73 years) with active left-sided ulcerative col itis ingested a Eudragit-coated gelatine capsule containing In-111-labelled amberlite resin on four successive days. Regional colonic distribution, tr ansit times and percentage of daily dose resident were calculated from the average of four serial gamma camera images on the 4th day. Results: (mean [95% CI]). When compared to controls, patients with colitis had significantly faster total colon transit (24.3 h [9.5-39.1] vs. 51.7 h [41.1-62.3]) as well as faster proximal colon transit (18.7 h [9.1-28.3] vs . 36.7 [28.5-44.9]), and distal colon transit (3.1 h [-0.5 to 6.8] vs. 15.0 h [10.5-19.5]), respectively (all P < 0.01). Material was asymmetrically d istributed in health (proximal colon 69% [63-76] vs. distal colon 31% [24-3 7]). This asymmetry was more extreme in colitis, with corresponding values of 91% [85-96] vs. 9% [4-15]. As a result colitics had less material in the left-sided colon (9% [4-15] vs. 31% [24-37]), P < 0.001. Colitics had a si gnificantly lower percentage of the daily dose resident within the left sid e of the colon compared to controls (13% [-2 to 28] vs. 63% [44-81]), P < 0 .01. Conclusions: Delayed release oral formulation is asymmetrically distributed within the colon in health. This asymmetry is exaggerated in active left-s ided ulcerative colitis and, together with faster colonic transit, results in reduced exposure of the distal colon to orally-dosed topical agents.