Imodium Mechanism of Action

Pharmacotherapeutic group: Antipropulsives. ATC code: A07 DA03.
Pharmacology: Pharmacodynamics: Loperamide binds to the opiate receptor in the gut wall. Consequently, it inhibits the release of acetylcholine and prostaglandins, thereby reducing propulsive peristalsis, and increasing intestinal transit time. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency.
Pharmacokinetics: Absorption: Most ingested loperamide is absorbed from the gut, but as a result of significant first pass metabolism, systemic bioavailability is only approximately 0.3%. Loperamide HCl formulations (hard and soft capsule, coated and uncoated tablet, chewable and orodispersable tablet, oral solution) are bioequivalent in terms of rate and extent of loperamide absorption.
Distribution: Studies on distribution in rats show a high affinity for the gut wall with a preference for binding to receptors of the longitudinal muscle layer. The plasma protein binding of loperamide is 95%, mainly to albumin. Non-clinical data have shown that loperamide is a P-glycoprotein substrate.
Metabolism: Loperamide is almost completely extracted by the liver, where it is predominantly metabolized, conjugated and excreted via the bile. Oxidative N-demethylation is the main metabolic pathway for loperamide, and is mediated mainly through CYP3A4 and CYP2C8. Due to this very high first pass effect, plasma concentrations of unchanged drug remain extremely low.
Excretion: The half-life of loperamide in man is about 11 hours with a range of 9-14 hours. Excretion of the unchanged loperamide and the metabolites mainly occurs through the faeces.
Paediatric Population: No pharmacokinetic studies were performed in the paediatric population. It is expected that pharmacokinetic behavior of loperamide and drug-drug interactions with loperamide will be similar to those in adults.