Pharmacology, Toxicology, Clinical Efficacy, and
Adverse Effects of Calcium Polycarbophil, An Enteral
Hydrosorptive Agent

Ivan E. Danhof, Ph.D., M.D.

Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. It is chemically and physiologically inert. In dilute alkali it possesses marked hydrophilic capacity (60 to 100 times its weight), which is the basis for its therapeutic use. In daily dosages of 4 to 5 g in adults, it appears to be quite safe, is non-toxic, does not interfere with digestion or absorption, and does not cause gastrointestinal irritation. It appears to be effective in the treatment of both constipation and diarrhea due to functional or organic causes. Several days of continuous use are necessary before effectiveness becomes apparent. Clinical studies, of which there are relatively few, range from uncontrolled, unblinded evaluations of an almost anecdotal nature to well controlled, double-blind, crossover studies. Additional carefully controlled studies on dietary influences, exercise, and patient compliance would be helpful. Adverse effects, which are minimal, include epigastric fullness or heaviness, abdominal distention and bloating, and flatulence. As with all bulk-forming agents, calcium polycarbophil should not be used by persons who have stenotic lesions of the gastrointestinal tract.

(Pharmacotherapy. 1982;2:18-28)

OUTLINE

Introduction

Clinical Pharmacology of Bulk-Forming Laxative Agents

Constipation

Hydrophilic Properties

Mechanical Properties

Metabolic Properties

Diarrhea

Polycarbophils

Polycarbophil

Calcium Polycarbophil

Relative Equivalence of Polycarbophil and

Calcium Polycarbophil

From the Department of Physiology, Southwestern Medical School, The University of Texas Health Science Center at Dallas.

Address reprint requests to Dr. Ivan E. Danhof at the Department of Physiology, University of Texas Health Science Center, 5323 Harry Hines Boulevard, Dallas, TX 75235.

Calcium Load

Toxicological Properties of Polycarbophil and

Calcium Polycarbophil

Acute Toxicity

Subacute Toxicity

Chronic Toxicity

Teratology

Overdose in Man

Clinical Studies

Normal Subjects

Nutritional Studies

Laxative/Enema-Dependent Bedridden Patients

Laxative/Enema-Dependent Ambulatory Patients

Chronic Constipation

Acute Diarrhea

Chronic Diarrhea

Adverse Effects

Precautions

Introduction

A substantial proportion of the population of the United States seems to be "bowel conscious" and preoccupied with bowel evacuatory patterns.¹ This view is corroborated by the large number of laxative products available, the number of advertisements for laxatives on radio and television and in newspapers and magazines, and the large expenditures for over-the- counter laxative medications; millions of dollars are spent annually for such products. Concern about bowel evacuation is not confined to lay consumers, since in most hospitals it is almost universal practice to order a pro re nata laxative for every patient upon admission.

Gastrointestinal stimulants are the most widely prescribed category of laxative agents (Table 1).¹ However, recently there has been renewed interest in the bulk-forming agents. In the 1920's, “dietary roughage" was promoted for normalization of bowel evacuatory function; in the late 1970's, a recrudescence of interest occurred that stressed an increased intake of "dietary fiber." However, changes in dietary habits are difficult to achieve on a permanent basis, and bulk laxatives have been used to supplement diets relatively deficient in dietary fiber. The newest bulk agent of current interest is calcium polycarbo- phil (Mitrolan,® A. H. Robins), although the efficacy of its parent compound, polycarbophil, was demonstrated more than two decades ago.⁴

Clinical Pharmacology of Bulk-Forming Laxative Agents

Action in Constipation

Bulk laxatives differ in the degree and manner in which the bowel evacuatory pattern is modified in the desired direction. Their pharmacological properties are as follows:

Hydrophilic properties. All bulk laxatives possess the property of "water-holding," which results in the formation of a gel through colloidal swelling.¹ The degree of hydrophilia varies considerably and may be influenced by the pH of the solution. Psyllium preparations, for example, absorb water equally well in acid and alkaline solutions and therefore permit colloidal swelling of the material in the stomach as well as in the small intestine; this may give rise to gastric distention and complaints of mid-epigastric fullness. This property may be utilized to advantage in controlling food intake in obese patients by prescribing psyllium products 20 to 30 minutes preprandially. Polycarbophil has limited hydrophilic activity in acid solutions and, accordingly, causes little gastric distention. Polycarbophil possesses a 3-4 fold greater hydrophilic capacity on a weight basis than psyllium preparations (Table 2).

Mechanical properties. When bulk laxatives are ingested along with water or other liquids, the resulting colloidal mass stimulates stretch receptors in the walls of the small intestine and colon. This action provides mechanical stimuli for both trituratory and propulsive bowel motor activity.¹ 

All bulk agents provide this type of physiological stimulation.

Metabolic properties. Non-synthetic bulk materials (bran, psyllium, cellulose) contain hemicelluloses. These substances may serve as substrates for the cellulose-splitting activities of the microflora in the colon of most animals, including man. Volatile, short-chain fatty acids (e.g., acetic, proprionic, butyric) are formed in the colon and excreted in high concentrations in the feces.⁸ At the pH of normal colonic contents [—5.5], volatile fatty acids are 99% ionized, possess low lipid solubility, and act osmotically to retain water in the fecal material.⁹ This results in softer fecal material that is more easily passed. The increased concentration of volatile fatty acids in the distal colon and rectum may cause increased stool frequency by acting on the intestinal smooth muscle of the lower tract along with an increase in bulk-related distention. Indeed, volatile fatty acids are probably responsible for controlling fecal bulk in normal persons.¹⁰

Bulk laxatives are generally well tolerated by patients, produce almost no mucosal irritation, modify fecal consistency in a desirable fashion, and are associated with little cramping, a prominent side effect of irritant laxatives. Some sense of epigastric heaviness or fullness may be present, and increased intestinal gas may be manifested by abdominal distention and flatulence. Bulk agents have the disadvantages of low intensity and slow onset of action; they often require several days of dosing before efficacy is noted.¹⁴-⁶

Diarrhea

Fecal consistency has been shown to be related to the water content of the stool. Normal feces have a water content of 65-80%,¹¹ and while showing variations from person to person, fecal water content is relatively uniform in a given individual.⁵'¹² A 10% difference in fecal water content may result in hard, inspissated, formed fecal scybala or unformed, water, diarrheal stools.¹² A 2-4% increase in fecal water content causes a considerable softening and increase in fluidity of feces.¹² Thus, the colloidal system in feces is very sensitive to a relatively small change in water content.²

The seemingly paradoxical use of hydrophilic colloids in the treatment of both diarrhea and constipation (Table 1), stems from the ability of bulk agents to modify the fecal colloidal system. In diarrheal states, the hydrophilic agents absorb free fecal water and produce a formed gel.² The gel, in contradistinction to free intraluminal water, resists translocation in the intestinal tract. This slower intestinal transit allows for increased absorption of water and electrolytes into the systemic circulation.¹³ The reduction in loss of fecal water and electrolytes may operate, at least on a theoretical basis, in the circumstance where the bowel fails to absorb water in an adequate manner, owing to intestinal hurry (decreased intestinal transit time) or mucosal absorptive dysfunction. Passage of a single, large volume, watery stool in a neonate or small infant may represent a hazardous degree of dehydration, which if not corrected anon, will result in clinically significant electrolyte imbalance.¹⁴ In contrast, in constipa- tory states, the hydrophilic agents retain water in the feces opposing the dehydrational forces of the bowel.

Polycarbophils

Polycarbophil

Polycarbophil is polyacrylic acid cross-linked with divinyl glycol. It is insoluble in water, dilute acids, and common organic solvents. When placed in dilute alkali, it absorbs at least 60 times its original weight⁷ and may absorb as much as 100 times its weight.⁵ This remarkable water-retaining capacity is the basis for its use as an enteral hydrosorptive agent that possesses the hydrophilic and mechanical properties of bulk agents. Since polycarbophil is inert, it is not metabolized by colonic micro-organisms. It does not cause formation of volatile fatty acids. Thus, polycarbophil does not have osmotic and stimulant properties, in contrast to other commonly used bulk agents. Owing to the lack of volatile fatty acid formation, the onset of effective laxative action of polycarbophil may be somewhat delayed in comparison with psyllium preparations.