Ileal brake

Infusion of fat into the ileum has been shown to cause a lengthening of the SITT—a phenomenon known as the ileal brake (27,28). However, the effect is generally modest (causing a delay of 30-60 min) and attempts to exploit this mechanism in drug delivery have had limited success. Dobson et al. (29,30) studied the effect of co-administered oleic acid on the small intestinal transit of non-disintegrating tablets. They showed a delay in SITT in over half of all cases, and a doubling of SITT in some instances, but in the other cases SITT was either unaffected or even reduced. Lin et al. (31) have also showed slowed GI transit in patients with chronic diarrhea by administration of emulsions containing 0, 1.6, and 3.2 g of oleic acid. Small intestinal transit in normal subjects was measured at 102 11 min, while the transit times in the patients treated with the three emulsions were, respectively, 29 3, 57 5 and 83 5 min. 

Spiller R. The ileal brake—inhibition of jejunal motility after ileal fat perfusion in man. Gut 1984 25 365-374. 

Dobson CL, Davis SS, Chauhan S, Sparrow RA, Wilding IR. The effect of oleic acid on the human ileal brake and its implications for small intestinal transit of tablet formulations. Pharm Res 1999 16 92-96. 

Read, N.W., A. McFarlane, R.I. Kinsman, and S.R. Bloom. 1984. The ileal brake A potent mechanism for feedback control of gastric emptying and small bowel transit. In Gastrointestinal motility, ed. C. Roman, 335. Lancaster MTP Press. 

There is evidence that, in humans, a luminal, protease-mediated, negative feedback system may be operative under certain circumstances (Slaff et al., 1984), but it is controversial whether (and rather unlikely that) this mechanism contributes to the pathogenesis of pain in patients with chronic pancreatitis. Several controlled therapeutic trials in patients with chronic pancreatitis have yielded conflicting results. Moreover, experimental data suggest that hormonally-induced inhibition of pancreatic secretion alone is ineffective in painful pancreatitis. It is more likely that amelioration of pain following enzyme administration originates from correction of disturbed motor function, such as ileal brake... 

Lipids such as oleic acid or its salts are reported to slow gastric emptying and also act as an ileal brake. This allows longer time for dissolution and absorption in the small intestine. " Citric acid and other organic acids also have been shown to slow gastric emptying. However, the levels required for such effects may be impractical for most dosage forms. 

Glucagon-derived peptides (GLP-1, GLP-2) are produced in L-cells of the intestinal mucosa of the ileum and colon (Holst 1997). GLP-1 inhibits gastric emptying. This may be the basis for its ability to increase satiety and reduce food intake in humans, thereby acting as an ileal brake hormone. The effects of GLP-2 have not been as clearly characterised as GLP-1. 

The rate of gastric emptying under fed conditions is controlled by the energy content of the meal, the energy requirement of the body, and feedback mechanisms including the ileal brake mechanism [33, 34]. Furthermore, the rate of gastric emptying of... 

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