2021-08-17
P. P. TOSKES*, K. L. CONNERY* & T. W. RITCHEY
DISCUSSION
A recent critique of controlled treatment trials in irritable bowel syndrome concludes that there is no convincing evidence that any therapy is effective in treating the entire irritable bowel syndrome symptom c0mp1ex. Therefore, treatment must be suited to the needs of the individual patient based on the presenting symptoms. In our study, calcium polycarbophil was strongly preferred by patients with a diagnosis that included constipation, by patients with symptoms that included bloating, and by patients with two or more symptoms. The data suggest that specific irritable bowel syndrome symptoms or combinations of symptoms can be managed with calcium polycarbophil and that patients with these symptoms can obtain substantial benefit from a treatment program that includes calcium polycarbophil.
At this time, we are not aware of any published studies that report the use of calcium polycarbophil in irritable bowel syndrome. The results of an unpublished study (available through FDA Dockets Branch) of 398 irritable bowel syndrome patients showed calcium polycarbophil to be statistically significantly more effectivethan placebo for the relief of abdominal pain and bowel trouble (twosided P = 0.02) at a dosage of 6 g/day.18 Improvement in abdominal pain and bowel trouble was dose-related and was particularly marked in patients with constipation as a major complaint. Highly significant improvement in these parameters also occurred in patients with constipation, a group that comprised nearly half the total study population. In the present study, all but two patients had a diagnosis that included constipation. The strong preference for polycarbophil expressed by patients with constipation and by patients with alternating diarrhoea and constipation is consistent with the unpublished study results and suggests that patients with symptoms that include constipation could benefit from calcium polycarbophil.
Calcium polycarbophil is not metabolized and has limited hydrophilic activity in acidic environments. Polycarbophil exerts its maximal hydrophilic action in the alkaline medium of the small intestine and and, consequently, causes little gastric distension. In experiments in dogs, polycarbophil meals produced the same level of small intestinal motor activity as salinecontrol meals and were associated with aborally directed jejunal contractions. In contrast, pectin and psyllium meals increased intestinal motor activity and produced irregular jejunal contractions. In addition, a recent preliminary study in irritable bowel syndrome patients demonstrated amelioration of abnormal small intestine motility following the administration of 6 g of calcium polycarbophil per day for two weeks. This was a placebo-controlled cross-over trial in which calcium polycarbophil increased the frequency of phase 3 contractions as determined by small intestine manometry to normal levels. Studies in humans have shown that calcium polycarbophil produces less flatulence and bloating than fibre laxatives while promoting laxation.2gIn our study, patients with symptoms that included bloating had a greater preference for polycarbophil than those without bloating. It is likely that polycarbophil would be better tolerated in patients with bloating as a major complaint than would a fermentable bulking agent, which might exacerbate bloating. Additional research indicates that calcium polycarbophil tablets may be more acceptable than other laxative formulations.23 The potential for greater compliance afforded by tablets provides an additional advantage in long-term treatment of irritable bowel syndrome.
The therapeutic role of dietary fibre and bulking agents in irritable bowel syndrome is not fully established. Clinical trials in irritable bowel syndrome are made difficult by the intermittent nature of the disease. At the same time, the interpretation of results obtained in treatment trials is hindered by the lack of objective efficacy parameters. In the present study, the retrospective analysis of patient subgroup preferences suggested a relationship between presenting symptoms and treatment preference. Because of the large placebo effect often observed in clinical studies of irritable bowel syndrome, the demonstration of statistically significant differences between treatment and placebo may be possible only with extremely Iarge study populations. For further investigations, we would consider the stratification of patients by symptomatology prior to entry to increase the comparability of the treatment groups for key symptoms. The results obtained in this type of study should facilitate a more accurate description of the patient most likely to benefit from the use of a bulking agent and serve to define the role of calcium polycarbophil and similar agents in irritable bowel syndrome.
ACKNOWLEDGEMENTS
The authors thank Mrs Mickie Alden for preparing the manuscript. The study was supported by a grant from Lederle Laboratories, Division of American Cyanamid, Pearl River, NY, USA
