Sign Out
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 lead to a lowering of pH in the colonic lumen and via an osmotic effect to an increase of the volume of the colonic contents. These effects stimulate the peristalsis of the colon and return the consistency of the stools. The constipation is cleared and the physiological rhythm of the colon is reinstated.
As a prebiotic substance, lactulose intensifies the growth of Bifidobacterium and Lactobacillus, while Clostridium and Escherichia coli may be suppressed. This may lead to alleviation of the constipation and, in this way, have a favorable effect on the patient's state of health.
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 the 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 however might serve as a model compound for other nitrogenous substances.
For bowel cleansing in preparation for colonoscopy, a regimen is proposed of bisacodyl (10mg) the evening before the colonoscopy and on the day of colonoscopy a 12.5% lactulose solution (m/m). Bisacodyl is a stimulant laxative and lactulose is an osmotic laxative. The pharmacodynamic effect consists of a strong cathartic effect and initiation of diarrhea. The bowel is subsequently emptied and cleansed.
Pharmacokinetics: Lactulose is poorly absorbed after oral administration and it reaches the colon unchanged. There it is metabolized by the colonic bacterial flora. Metabolism is complete at doses 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.
