title: Limited exposure of the healthy distal colon to orally-dosed formulation is further exaggerated in active left-sided ulcerative colitis.
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.
authors.affiliation: Department of Gastroenterology, Queens Medical Centre, Nottingham, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Hebden
authors.forename: P E
authors.initials: PE
authors.lastname: Blackshaw
authors.forename: A C
authors.initials: AC
authors.lastname: Perkins
authors.forename: C G
authors.initials: CG
authors.lastname: Wilson
authors.forename: R C
authors.initials: RC
authors.lastname: Spiller
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002214:Capsules / Q000493:pharmacokinetics; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D005260:Female; D005772:Gastrointestinal Transit; D006801:Humans; D008297:Male; D008875:Middle Aged; D011109:Polymethacrylic Acids / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D012117:Resins, Synthetic / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D012117:Resins, Synthetic; C038300:methylmethacrylate-methacrylic acid copolymer; C046797:amberlite