Therapeutic effects of loxiglumide, a cholecystokinin antagonist, on chronic constipation in elderly patients: a prospective, randomized, double‐blind, controlled trial

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Abstract
Severe chronic constipation is a common health problem, particularly among elderly nursing‐home patients. Cholecystokinin (CCK) is involved in the regulation of colonic motility, and the blockade of CCKA receptors with loxiglumide, a potent and highly specific CCKA antagonist, dramatically accelerates colonic transit time in healthy human volunteers. The effect of loxiglumide on the bowel habits and colonic transit time in 21 chronically constipated nursing‐home patients (mean age 83, range 71–89 years) was studied in a randomized, placebo‐controlled, double‐blind cross‐over study. Loxiglumide 800 mg t.i.d. or identical‐looking placebo tablets were given orally in sequence with a 7‐day washout period in between for 21 days each. The number of spontaneous bowel movements and that of administered enemas was recorded for each 3‐week phase. At the end of each treatment period colonic transit time was assessed using radio‐opaque markers. Treatment with loxiglumide significantly (P < 0.005) accelerated colonic transit time from 113 ± 6 to 81 ± 10 h. The frequency of weekly bowel movements increased from 3.9 ± 0.5 (placebo) to 4.9 ± 0.5 (loxiglumide) (P < 0.006), while the number of enemas over the 3 weeks decreased from 2.7 ± 0.6 to 1.3 ± 0.4 for placebo and loxiglumide, respectively (P < 0.005). No serious side‐effects were observed and there were no signs of exocrine pancreatic insufficiency induced by loxiglumide. The blockade of CCKA receptors with loxiglumide significantly improves chronic constipation in geriatric patients. Loxiglumide may therefore constitute the prototype of a new class of potent therapeutic agents effective in the treatment of constipation.