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Pharmacotherapeutic group: Osmotically acting laxatives. ATC code: A 06A D11.
Pharmacology: Pharmacodynamics: In the colon lactulose is broken down by colonic bacteria into low-molecular organic acids. These acids lower the pH in the colonic lumen and increase the volume of the colonic contents via an osmotic effect. These effects stimulate the peristalsis of the colon and return consistency to the stool. Constipation is corrected and the physiological rhythm of the colon is reinstated.
In hepatic encephalopathy (HE), the effect has been attributed to: suppression of proteolytic bacteria by an increase of acidophilic bacteria (e.g. lactobacillus), trapping of ammonia in the ionic form by acidification of the colonic contents, catharsis due to the low pH in the colon as well as an osmotic effect and alteration of bacterial nitrogen metabolism by stimulating the bacteria to utilize ammonia for bacterial protein synthesis. Within this context, however, it should be realized that hyperammonemia alone cannot explain the neuropsychiatric manifestations of HE. The ammonia might, however, serve as a model compound for other nitrogenous substances.
Lactulose as a prebiotic substance promotes the growth of normal flora, like Bifidobacterium and lactobacillus.
Pharmacokinetics: Lactulose is poorly absorbed after oral administration and reaches the colon unchanged. There it is metabolised by the colonic bacterial flora. Metabolism is complete at dose up to 25 - 50 g or 40 - 75 ml; at higher dosages, a proportion may be excreted unchanged.
Toxicology: Preclinical safety data: The results of acute, sub-chronic and chronic toxicity studies in various species indicate that the compound has very low toxicity. The effects observed, appear to be more related to the effect of bulk in the gastrointestinal tract than to a more specific toxic activity.
In reproduction and teratology experiments in rabbits, rats or mice no adverse effects were found.
