מתוך medicontext.co.il
LONDON (Reuters Health) – By virtue of its acceleration of intestinal transit, cisapride may help prevent the gallstone-promoting effects of octreotide, according to a report in the December issue of Gut.
Octreotide, a long-acting analogue of somatostatin used to treat acromegaly, inhibits gall bladder emptying and prolongs intestinal transit, the authors explain, resulting in an increased incidence of gall bladder stones.
Dr. R. Hermon Dowling, from Kings College in London, and colleagues sought to determine whether cisapride treatment (10 mg four times daily for 2 weeks) could overcome these adverse effects of octreotide.
They found it "had no prokinetic effect on the gallbladder." Normal individuals and acromegalic patients not receiving octreotide experienced higher fasting and residual gall bladder volumes during cisapride treatment, the authors report, but delta volume, ejection fraction, and gall bladder emptying rate remained unchanged.
Acromegalic patients taking octreotide, however, showed significantly greater rates of gall bladder emptying during cisapride treatment than while receiving placebo, the report indicates. They also experienced higher fasting, residual, and delta gall bladder volumes, but ejection fractions did not improve with cisapride therapy.
Cisapride consistently reduced the mouth to caecum transit time and the large bowel transit time in all patients and healthy controls, the researchers note, and cisapride treatment brought a significant reduction in the mean proportion of deoxycholic acid (DCA) in fasting serum.
In fact, large bowel transit times were linearly related to DCA proportions in fasting serum, the results indicate.
"What we have shown (I hope convincingly) is that 2 weeks cisapride treatment of acromegalic patients on long-term octreotide will counter the adverse effects of octreotide on both intestinal transit and the percent DCA in serum," Dr. Dowling told Reuters Health. "Intestinal transit is now firmly established as a pathogenetic mechanism in cholesterol gallbladder stone formation, and by countering the prolonged colonic transit we have, potentially, a logical means of preventing stone formation in high-risk groups."
Clinical trials of cisapride for this purpose are unlikely. "In the US, Britain, and elsewhere," Dr. Dowling said, "cisapride itself has been withdrawn from the market due to concerns about its cardiotoxicity, and new generation 'enterokinetics' (ideally colon-specific) have still to be approved."
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