LACTULOSE

Chemistry - A synthetic derivative of lactose, lactulose is a disaccharide containing one molecule of galactose and one molecule of fructose. It occurs as a white powder that is very slightly soluble in alcohol and very soluble in water. The commercially available solutions are viscous, sweet liquids with an adjusted pH of 3-7.

Storage, Stability, Compatibility

Lactulose syrup should be stored in tight containers, preferably at room temperature; avoid freezing. If exposed to heat or light, darkening or cloudiness of the solution may occur, but apparently does not affect drug potency.

Pharmacology - LACTULOSE

Lactulose is a disaccharide (galactose/fructose) that is not hydrolyzable bymammalian and, probably, avian gut enzymes. Upon reaching the colon, lactulose is metabolized bythe resident bacteria resulting in the formation of low molecular weight acids (lactic, formic, acetic)and CO2. These acids have a dual effect; they increase osmotic pressure drawing water into thebowel causing a laxative effect and also acidify colonic contents. The acidification causes ammonia
NH3 (ammonia) to migrate from the blood into the colon where it is trapped as [NH4]+(ammonium ion) and expelled with the feces.
Uses, Indications - The primary use of lactulose in veterinary medicine is to reduce ammonia blood levels in the prevention and treatment of hepatic encephalopathy (portal-systemic encephalopathy; PSE) in small animals and pet birds. It is also used as a laxative in small animals.

Pharmacokinetics - LACTULOSE

In humans, less than 3% of an oral dose of lactulose in absorbed (in the smallintestine). The absorbed drug is not metabolized and is excreted unchanged in the urine within 24hours.
Contraindications/Precautions - Lactulose syrup contains some free lactose and galactose, andmay alter the insulin requirements in diabetic patients. In patients with preexisting fluid andelectrolyte imbalances, lactulose may exacerbate these conditions if it causes diarrhea; use cautiously.

Adverse Effects, Warnings

Symptoms of flatulence, gastric distention, cramping, etc. are notuncommon early in therapy, but generally abate with time. Diarrhea and dehydration are symptomsof overdosage; dosage should be reduced.
Cats dislike the taste of lactulose and administration may be difficult.
Overdosage - Excessive doses may cause flatulence, diarrhea, cramping and dehydration. Replacefluids and electrolytes if necessary.

Drug Interactions

Do not use lactulose with other laxatives as the loose stools that are formedcan be falsely attributed to the lactulose with resultant inadequate therapy for hepatic encephalopathy.
Theoretically, orally administered antibiotics (e.g., neomycin) could eliminate the bacteria responsible for metabolizing lactulose, thereby reducing its efficacy. However some data suggests that synergy may occur when lactulose is used with an oral antibiotic (e.g., neomycin) for the treatment of hepatic encephalopathy. Enhanced monitoring of lactulose efficacy is probably warranted in cases where an oral antibiotic is added to the therapy.
Oral antacids (non-adsorbable) may reduce the colonic acidification effects (efficacy) of lactulose.