Effect of cyclooxygenase‐2 inhibitors on gastric emptying and small intestinal transit in humans

Abstract

Endogenous prostaglandins regulate smooth muscle activity; prostaglandins and cyclooxygenase (COX) inhibitors influence gastrointestinal motility in inflammatory states such as postoperative ileus in animal models. The objective of this study was to evaluate the effects of two COX-2 inhibitors on gastric emptying and intestinal transit in healthy humans. In a double-blind, placebo-controlled, parallel-group study, 66 healthy volunteers were randomized to one of two commercially available oral COX-2 inhibitors (celecoxib and rofecoxib), cisapride (positive control), or placebo. Following 7 days on therapy, study participants underwent a test of gastric emptying and small bowel transit of liquids and solids using scintigraphy. Data were analysed using Kruskal-Wallis (ANOVA on ranks)and Mann-Whitney rank sum tests. There were significant group effects on transit of solids: gastric emptying (ANOVA, P = 0.005) and small bowel transit (ANOVA, P = 0.056). However, neither COX-2 inhibitor significantly accelerated the liquid or solid gastric emptying or small bowel transit compared with placebo. The positive control, cisapride, accelerated gastric emptying of solids (post-lag slope of gastric emptying, P < 0.05), and small bowel transit of solids (t10%, P = 0.016). At maximum clinically approved dosages, celecoxib and rofecoxib have no significant effects on gastric emptying or small intestinal transit in healthy humans. Cisapride accelerates gastric emptying and small bowel transit in healthy humans.

Gastroprotection Studies of Schiff Base Zinc (II) Derivative Complex against Acute Superficial Hemorrhagic Mucosal Lesions in Rats

“…The involvement of formation of PGE-2 in the gastroprotective mechanisms was previously investigated with conflicting evidences [25], [29], [33], [34]. PGE-2, the most abundant GI prostaglandin, is fundamentally important in the regulation of gastric mucus secretion [78], gastric acid secretion [79] and gastric motility [80], [81]. In oral administration of ethanol, reduction in formation of PGE-2 lessened acid secretion and gastric motility [78], and decreased gastric mucus secretion [82].…”

Postoperative ileus: strategies for reduction

“…Those studies that have shown a benefi t in using COX-2 inhibitors have not been able to demonstrate that the reduction in POI is independent of the subsequent reduction in opioid use. The main benefi t of these drugs has been their ability to lower the total dose of narcotics needed for adequate pain control (Bouras et al 2004;Sim et al 2007). Similar trials have occurred using the intravenous anti-infl ammatory drug, ketorolac.…”

Examining Small Intestinal Transit Time as a Function of Age: Is There Evidence to Support Age-Dependent Differences among Children?

“…Correspondingly, 52 subject groups were included within the analysis. The analysis included 11 investigations (Davis et al, 1984a(Davis et al, ,b, 1986a(Davis et al, , 1987Khosla et al, 1989;Madsen and Jensen, 1989;Coupe et al, 1991;Madsen, 1992;Billa et al, 2000;Bouras et al, 2004;Fadda et al, 2009), where estimates of intestinal transit were pooled between test conditions (e.g., fasted versus fed). For each of these investigations, mean intestinal transit times were not found to be significantly different between treatment arms as either denoted by the authors' results or independently confirmed using a paired Student's t test (P .…”