Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs.
Measurements of luminal pH in the normal gastrointestinal tract have shown a progressive increase in pH from the duodenum to the terminal ileum, a decrease in the caecum, and then a slow rise along the colon to the rectum. Some data in patients with ulcerative colitis suggest a substantial reduction below normal values in the right colon, while limited results in Crohn's disease have been contradictory. Determinants of luminal pH in the colon include mucosal bicarbonate and lactate production, bacterial fermentation of carbohydrates and mucosal absorption of short chain fatty acids, and possibly intestinal transit. Alterations in these factors, as a result of mucosal disease and changes in diet, are likely to explain abnormal pH measurements in inflammatory bowel disease (IBD). It is conceivable that reduced intracolonic pH in active ulcerative colitis impairs bioavailability of 5-aminosalicylic acid from pH dependent release formulations (Asacol, Salofalk) and those requiring cleavage by bacterial azo reductase (sulphasalazine, olsalazine, balsalazide), but further pharmacokinetic studies are needed to confirm this possibility. Reports that balsalazide and olsalazine may be more efficacious in active and quiescent ulcerative colitis, respectively, than Asacol suggest that low pH may be a more critical factor in patients taking directly pH dependent release than azo bonded preparations. Reduced intracolonic pH also needs to be considered in the development of pH dependent colonic release formulations of budesonide and azathioprine for use in ulcerative and Crohn's colitis. This paper reviews methods for measuring gut pH, its changes in IBD, and how these may influence current and future therapies.
Nugent
S G
SG
Department of Surgery, St George's Hospital Blackshaw Road, London, UK.
Kumar
D
D
Rampton
D S
DS
Evans
D F
DF
D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001379:Azathioprine / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D019819:Budesonide / Q000493:pharmacokinetics / Q000627:therapeutic use; D002404:Catheterization; D004566:Electrodes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism*; D019804:Mesalamine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012016:Reference Values; D013686:Telemetry
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D019804:Mesalamine; D019819:Budesonide; D001379:Azathioprine