Drug intelligence / Profile preview

L-ornithine-L-aspartate + lactulose

Development stage
Unknown
Lead developer
Merz Therapeutics
Modality
Small Molecules
Administration
Oral, Intravenous
01

Overview

L-ornithine-L-aspartate + lactulose is a combination therapy used primarily for the treatment of hepatic encephalopathy (HE), a neuropsychiatric complication of advanced liver disease. This combination leverages two complementary mechanisms to reduce blood ammonia levels, which are central to the pathogenesis of HE. L-ornithine-L-aspartate (LOLA) is a salt formed from the amino acids ornithine and aspartic acid. It acts by enhancing ammonia detoxification through two main pathways in the liver: - Stimulating the urea cycle in periportal hepatocytes, thereby increasing conversion of ammonia to urea. - Promoting glutamine synthesis via activation of glutamine synthetase in perivenous hepatocytes and skeletal muscle[5][9]. Lactulose is a nonabsorbable disaccharide that works by acidifying colonic contents after bacterial fermentation. This process traps ammonia as ammonium ions (NH4+) in the gut, reducing its absorption into systemic circulation. Lactulose also acts as an osmotic laxative, increasing fecal nitrogen excretion and altering gut microbiota composition to favor non-ammoniagenic bacteria[7][8]. Clinical studies and meta-analyses have shown that this combination is more effective than lactulose alone at improving clinical outcomes in patients with hepatic encephalopathy—demonstrating higher rates of symptom resolution, greater reductions in blood ammonia levels, improved liver function markers (AST, ALT, TBIL), shorter recovery times from HE episodes, and lower short-term mortality[1][2][8]. The combination may also provide additional hepatoprotective effects due to LOLA’s antioxidant properties[9].

Other names
LOLA + lactuloseL-ornithine L-aspartate and lactulose
02

Targets

UCE (Urea cycle enzymes)GLUL (Glutamine synthetase)

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