THE EFFECT OF PHARMACOLOGICAL MODIFICATION OF GASTRIC-EMPTYING AND MOUTH-TO-CECUM TRANSIT-TIME ON THE ABSORPTION OF SUGAR PROBE MARKER MOLECULES OF INTESTINAL PERMEABILITY IN NORMAL MAN

Abstract. The present study examined the hypothesis that altered motility of the gastrointestinal tract affects absorption of probe markers of intestinal permeability. Seven healthy subjects, aged 32–44 years, received saline, 600 μg atropine or 10 mg metoclopramide in randomized order at weekly intervals. After 10 min they ingested a test solution containing 5 g lactulose, 5 g mannitol and 2 g 3‐O‐methyl glucose in 100 ml tap water. The molarity of the solution was 542 mmol l‐1 and the dose administered was 80 ml m‐2 body surface area. Gastric emptying was measured by ultrasound, mouth‐to‐caecum transit time by breath hydrogen analysis and sugar concentrations by gas‐liquid chromatography. Gastric emptying half‐times (min) were [mean (95% confidence intervals)] 14.9 (11.4–18.5) after saline, 22 (18.7–25.2) after atropine and 10.3 (7.0 12.6) after metoclopramide (P< 0.002). Transit times (min) were 68.9 (52–85.2) after saline, 143 (126–159) after atropine and 38 (21.2–54.5) after metoclopramide; P<0.0001. Analysis of plasma levels of mannitol and 3‐O‐methyl glucose showed a significant within‐subject effect of drug with time (P<0.03). Urinary excretion of mannitol in the first 5 h after ingestion of the test solution was 1256 (974–1620) mg after saline, 1560 (1210–2013) mg after atropine and 955 (740–1232) mg after metoclopramide (P<0.03). There were no significant differences in lactulose and 3‐O‐methyl glucose urinary excretion between drug treatments. Gastric emptying time was significantly correlated with mannitol excretion (P< 0.003) and lactulose excretion (P<0.03). There were no significant differences in lactulose:mannitol excretion ratios between treatments. Copyright © 1990, Wiley Blackwell. All rights reserved