Physiological and pathophysiological effects on small bowel transit

It has been reported that severe exercise delays the gastric emptying of food whereas moderate exercise accelerates it. In spite of these findings, exercise has little effect on the small intestinal transit of pellets given to fasted individuals22. Larger objects such as radioopaque markers showed a marked reduction in whole gut transit time following moderate exercise (jogging and cycling)23.

In cases of accelerated gastrointestinal transit, administration of a drug in a controlled release formulation instead of a conventional formulation may cause a higher fraction of the dose to escape absorption in the small intestine and enter the colon. This can reduce the availability of the drug either because of slow and erratic absorption or because of inactivation by colonic bacteria (Table 6.1). In contrast, diseases that retard small bowel transit could increase the bioavailability of drugs that are released slowly from controlled-release forms; however, conditions that encourage the overgrowth of bacteria in the small intestine could reduce the bioavailability of drugs susceptible to bacterial degradation (e.g. digoxin).

In patients with partial intestinal obstruction or a narrowed lumen, a single unit may lodge in the gut and expose the intestinal mucosa to high concentrations of drug which may lead to gastric irritation, bleeding, and even perforation24-26. For patients with this disease, multiparticulate formulations provide an advantage, because even if pellets lodged within the gut, they would do so over a wide area as they are well dispersed. In addition, each pellet

Table 6.1 Disease causing accelerated and decreased small intestinal transit times (S.I.T.T.)

Faster S.I.T.T.

Slower S.I.T.T.

Secretory diarrhoea

Constipation

Thyrotoxicosis

Myxoedema

Irritable bowel syndrome

Pseudo-obstruction

Chronic pancreatitis

Ileal resection

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