Lactulose

Lactulose is a non-absorbable two-sugar (disaccharide) consisting of the two simple sugars D-galactose and fructose. It does not occur naturally and must therefore be produced synthetically. Lactulose is used to treat constipation and hepatic encephalopathy. It is taken orally for constipation and either orally or rectally for hepatic encephalopathy.

Lactulose was first characterized and manufactured in 1929. Its medicinal effects were discovered and described a short time later by the Austrian chemist Friedrich Petuely. Lactulose has been used medicinally since about the 1950s. The drug is on the World Health Organization's list of essential medicines.

Pharmacodynamics

Constipation

Lactulose cannot be absorbed in the human small intestine and is not broken down by human enzymes, so the substance passes through the digestive tract unchanged. Lactulose is osmotically active, drawing water into the intestinal lumen. This results in softer and more easily excreted stools. Another laxative effect is produced by the fermentation of lactulose by intestinal bacteria in the colon. During this process, osmotically active and peristaltic stimulating substances are formed (e.g. acetate), but methane is also produced, which can sometimes lead to flatulence.

Hepatic encephalopathy

Lactulose is also converted in the large intestine by the bacterial flora into acids, mainly lactic and acetic acids. These cause acidification of the intestinal contents (increasing the H⁺ concentration in the intestine). This favors the formation of the non-absorbable ammonium ion (NH⁺₄) from ammonia (NH₃), which prevents NH₃ from entering the blood from the colon. Overall, this reduces the ammonia concentration in the plasma. Lactulose is therefore effective in the treatment of hepatic encephalopathy, which is favored by elevated plasma NH₃ levels.

Pharmacokinetics

After oral administration, less than 3% of the administered dose is absorbed in the small intestine. The remaining lactulose enters the large intestine, where it is partially metabolized. Even after metabolism, however, absorption of unchanged lactulose and its metabolites via the colon is negligible. Lactulose is essentially metabolized only in the colon by the saccharolytic bacteria present there. In particular, the substance is broken down into lactic acid and small amounts of acetic and formic acid. Renal excretion of the absorbed lactulose fraction has been shown to be about 3% and generally takes less than 24 hours. Most of the unabsorbed lactulose portion is excreted in the feces. Due to the low absorption, there are no reliable values for half-life, plasma protein binding, clearance and volume of distribution of the substance.

Side effects

Common side effects of lactulose are abdominal cramps, bowel sounds, and flatulence. Uncommon side effects include nausea and vomiting, hypokalemia with muscle weakness, constipation, and cardiac arrhythmias.

Toxicological Data

LD50, rat, oral: 18.16 g/kg