Background:
5‐Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating.
Aim:
To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5‐amino salicylic acid in the intestinal lumen.
Methods:
Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn’s disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease).
Results:
The median gastric pH values in the patient groups (Crohn’s disease 2.4, range 1.5–4.1; ulcerative colitis 1.95, range 1.55–4.4) were significantly higher than those observed in the controls (1.55, range 0.95–2.6). In the small bowel and colonic segments, all the pH values of Crohn’s disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission.
Conclusions:
The luminal release of 5‐amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.
Enteric-coated tablets leave the stomach mainly during the interdigestive phase. Composition as well as time of ingestion of meals may influence their gastric emptying considerably. In 12 normal volunteers gastric emptying of a plastic tablet with a metal core was followed by a metal detector in relation to different compositions and various times of ingestion of meals. With an empty stomach and after ingestion of 250 ml water, the mean time for gastric emptying of the tablet was 38 +/- 11 min (mean +/- SEM) and 38 +/- 8 min. Two hundred fifty milliliters of milk (652 kJ) and a formula diet (1000 kJ) delayed gastric emptying time to 128 +/- 14 and 152 +/- 6 min, respectively (P less than 0.05). Breakfast (2200 kJ) further retarded gastric emptying compared with both liquids to 249 +/- 24 min (P less than 0.05). There was a close correlation between nutritive density and gastric emptying of the tablet (r = 0.92; P less than 0.001). Main meals also delayed gastric emptying of tablets when compared to empty stomach (P less than 0.05). A snack after breakfast further delayed gastric emptying from 201 +/- 10 to 278 +/- 19 min (P less than 0.05). The largest delay was observed following ingestion of breakfast, lunch, dinner, and additional snacks (509 +/- 220 min). We conclude that the delay of gastric emptying of enteric-coated tablets by food is related to its nutritive density and eating habits. The gastric emptying of an enteric coated tablet that is ingested early in the morning may be delayed until late at night when several meals and snacks are ingested during the day, leading to unwanted alterations in bioavailability and to possible adverse effects.
SUMMARY
Aim and methods: To study the effect of 45 g lactose, 30 g lactulose and 10 mg bisacodyl on gastrointestinal transit in 30 healthy volunteers by metal detector and Hinton marker method. The first set of measurements were performed under standard conditions. In a second stage, transit was slowed to twice the original value by loperamide to simulate constipation conditions.
Results: Bisacodyl drastically accelerated small and large intestinal transit. Colonic transit was shortened to 23 % and to 31% of control values, without and with loperamide. Bisacodyl increased stool weight and decreased stool consistency in all persons. Lactulose marginally shortened small intestinal transit (P= 0.08) but significantly increased stool weight and decreased stool consistency. The accelerating effect of lactose on small intestinal transit was abolished by loperamide. Lactose did not influence colonic transit, stool weight or stool consistency. Results of metal detector and Hinton marker method corresponded well (r=0.75), the metal detector method measuring slightly shorter transit times than the Hinton marker method.
Conclusions: With the dose chosen in this trial, lactose did not have any laxative effect in lactose tolerant persons. Laxative effect was mild with lactulose and most pronounced with bisacodyl.
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