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

Clive Wilson, John Hebden, Elaine Blackshaw, Alan Perkins, Robin Spiller

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)

Abstract

Background: Active distal ulcerative colitis is often resistant to topically acting oral formulations. We speculated that the left side of the colon is underexposed to orally-dosed topical agents in patients with active distal 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 colitis ingested a Eudragit-coated gelatine capsule containing 111In-labelled amberlite resin on four successive days. Regional colonic distribution, transit 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 distributed in health (proximal colon 69% [63–76] vs. distal colon 31% [24–37]). 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 significantly lower percentage of the daily dose resident within the left side 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-sided ulcerative colitis and, together with faster colonic transit, results in reduced exposure of the distal colon to orally-dosed topical agents.
Original languageEnglish
Pages (from-to)155-161
Number of pages6
JournalAlimentary Pharmacology and Therapeutics
Volume14
Issue number2
DOIs
Publication statusPublished - 28 Feb 2000

Keywords

  • distal ulcerative colitis
  • topically acting oral formulations
  • oral therapy
  • ulcerative colitis

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