In vitro and animal studies show that IMODIUM® (loperamide hydrochloride) acts by slowing intestinal motility and by affecting water and electrolyte movement through the bowel. Loperamide binds to the opiate receptor in the gut wall. Consequently, it inhibits the release of acetylcholine and prostaglandins, thereby reducing peristalsis, and increasing intestinal transit time. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency.

In man, IMODIUM® prolongs the transit time of the intestinal contents. It reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. Tolerance to the antidiarrheal effect has not been observed. Clinical studies have indicated that the apparent elimination half-life of loperamide in man is 10.8 hours with a range of 9.1 - 14.4 hours. Plasma levels of unchanged drug remain below 2 nanograms per mL after the intake of a 2mg capsule of IMODIUM®. Plasma levels are highest approximately five hours after administration of the capsule and 2.5 hours after the liquid. The peak plasma levels of loperamide were similar for both formulations. Elimination of loperamide mainly occurs by oxidative N-demethylation. Cytochrome P450 (CYP450) isozymes, CYP2C8 and CYP3A4, are thought to play an important role in loperamide N-demethylation process since quercetin (CYP2C8 inhibitor) and ketoconazole (CYP3A4 inhibitor) significantly inhibited the N- demethylation process in vitro by 40% and 90%, respectively. In addition, CYP2B6 and CYP2D6 appear to play a minor role in loperamide N-demethylation. Excretion of the unchanged loperamide and its metabolites mainly occurs through the feces. In those patients in whom biochemical and hematological parameters were monitored during clinical trials, no trends toward abnormality during IMODIUM® therapy were noted. Similarly, urinalyses, EKG and clinical ophthalmological examinations did not show trends toward abnormality.

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