misoprostol and Cystic-Fibrosis

Seventeen children with cystic fibrosis were studied in a 6-week double-blind, placebo-controlled, crossover trial to determine the efficacy of misoprostol, 100 micrograms, four times a day, in improving fat absorption in patients already on pancreatic enzyme therapy. In those patients who had greater than 90% absorption on enzyme therapy alone, no further significant increase in absorption was achieved with misoprostol administration. Those patients who had absorption of less than 90% on standard enzyme therapy showed a significant improvement with misoprostol administration (p less than 0.01). One patient had a significant elevation in the eosinophil count during the period of misoprostol administration, but there were no significant changes in any other hematological or biochemical parameter. Misoprostol appears to be of benefit to those children with cystic fibrosis who have residual malabsorption on standard enzyme therapy.

Topics: Alprostadil; Anti-Ulcer Agents; Child; Clinical Trials as Topic; Cystic Fibrosis; Double-Blind Method; Drug Administration Schedule; Female; Humans; Intestinal Absorption; Male; Misoprostol; Placebos

Eleven cystic fibrosis children (mean age, 9.6 years) were chosen at random to participate in a study to observe the effects of concurrently stimulating gastric/duodenal bicarbonate secretion and inhibiting gastric acid secretion, using a methylated prostaglandin E1 analogue in patients with pancreatic insufficiency and taking pancreatic enzymes. Percentage fat absorption in 3-day stool collections were calculated before and after commencing therapy with misoprostol, 400 micrograms/day in divided doses. We found a significant reduction in fat output (14.7 +/- 11.7 versus 7.5 +/- 3.5 g/day, p less than 0.05) in the study group as a whole and a significant reduction in steatorrhoeic level as a percentage of fat intake in all of the patients with abnormal base-line collections (23.1% versus 9.2%, p less than 0.002). We conclude that misoprostol should be considered in cystic fibrosis patients with steatorrhoea as a means of improving nutrient absorption.

Topics: Alprostadil; Celiac Disease; Child; Clinical Trials as Topic; Cystic Fibrosis; Female; Humans; Intestinal Absorption; Male; Misoprostol; Pancreatin; Random Allocation

Misoprostol, a synthetic prostaglandin that is known to reduce gastric acid production and stimulate duodenal bicarbonate production, was evaluated in 22 patients with cystic fibrosis. In those patients who had greater than 10% fat malabsorption while taking pancrease the addition of misoprostol significantly reduced the degree of fat malabsorption.

Topics: Alprostadil; Anti-Ulcer Agents; Child; Child, Preschool; Cystic Fibrosis; Dietary Fats; Female; Humans; Infant; Intestinal Absorption; Male; Misoprostol; Pancreatin

In normal intestine, cyclic nucleotides (adenosine 3',5'-cyclic monophosphate [cAMP], guanosine 3',5'-cyclic monophosphate) and Ca(2+) inhibit neutral sodium absorption. In contrast, in the jejunum of a knockout mouse model of cystic fibrosis (CF), agents that elevate intracellular cAMP levels did not inhibit neutral sodium absorption, suggesting that the antiabsorptive effect of cAMP is dependent on the cystic fibrosis transmembrane conductance regulator (CFTR). The aim of the present study was to determine if a prostaglandin E(1) analogue, which causes elevation of intracellular cAMP and Ca(2+) levels, inhibits neutral sodium absorption in patients with CF in vivo.. Electrolyte and water absorption/secretion was measured during steady state perfusion of the jejunum with a balanced electrolyte solution. Patients with CF and healthy subjects were studied under basal conditions and during intraluminal infusion of a prostaglandin E(1) analogue (misoprostol).. The rate of neutral sodium absorption in the basal state was similar in healthy subjects and patients with CF. Prostaglandin infusion markedly reduced neutral sodium absorption in both healthy subjects and patients with CF. Prostaglandin caused high rates of electrolyte and water secretion in healthy subjects but only trivial rates of secretion in patients with CF.. CFTR mutations causing CF in humans do not prevent prostaglandin E(1) inhibition of neutral sodium absorption, even though these mutations produce a severe defect in prostaglandin-stimulated electrolyte secretion. These findings suggest that an intact antiabsorptive response to either cAMP or Ca(2+) may contribute to the relatively low level of intestinal disease in patients with CF.

Topics: Adolescent; Adult; Animals; Biological Transport; Cystic Fibrosis; Female; Gastrointestinal Agents; Humans; Intestinal Absorption; Jejunum; Male; Mice; Misoprostol; Prostaglandins E, Synthetic; Sodium; Water-Electrolyte Balance

To investigate the relationship between duodenal pH levels and supplemental pancreatic enzyme function in cystic fibrosis, 18 children with this condition had pH recordings performed from the second and fourth part of the duodenum. Compared to age-matched controls, patients with cystic fibrosis had significantly longer periods below a pH of 4.0 in the postprandial period and significantly less time above pH 5.8. These values correspond to the pH levels at which lipase is irreversibly destroyed (pH 4.0) and enteric coating of enzyme supplements dissolves (pH 5.8). A significant relationship was found between the pH recordings from the fourth part of the duodenum and the degree of residual fat malabsorption while taking enteric-coated enzyme supplements. Four patients with an excessively acidic duodenum and residual fat malabsorption despite high-dose enzyme supplementation were treated with misoprostol (Searle), a known acid-reducing agent. There were significant improvements in both duodenal pH values and fat absorption. We conclude that there is a wide range of duodenal pH values found in patients with cystic fibrosis and that the efficiency with which enzyme supplements work is closely related to these pH levels. Administration of misoprostol to those patients with excessively acidic duodenal pH levels as well as residual malabsorption appears to be of benefit in improving both the excessively acidic pH levels and the fat malabsorption.

Topics: Acid-Base Equilibrium; Adolescent; Alprostadil; Anti-Ulcer Agents; Child; Cystic Fibrosis; Dietary Fats; Duodenum; Humans; Intestinal Absorption; Malabsorption Syndromes; Male; Misoprostol; Pancreas