L-ornithine l-aspartate (LOLA) has been widely used as a treatment of hepatic encephalopathy due to its ammonia-lowering action. It is a mixture of two endogenous amino acids, l-ornithine and l-aspartate and may be administered either orally or parenterally. In this article, the authors have discussed the pharmacokinetics and pharmacodynamics of LOLA. 

The constituent amino acids are quickly absorbed by active transport, distributed and metabolized. Following IV administration, the absorption occurs in a biphasic pattern with a fast distribution phase and a slower terminal elimination phase. Peak level of l-ornithine, 10 times basal levels, is reached in 30 minutes and declines to normal within 7 hours. After oral administration, the peak level of l-ornithine, 5 times basal levels, occurs within 30–60 minutes and fall to baseline in 7 hours. The bioavailability is 82.2% after IV or oral administration. 

L-ornithine participates in the urea cycle in the periportal hepatocytes and it is transaminated to glutamate, similar to l-aspartate, in perivenous hepatocytes, skeletal muscle and brain. Through these metabolic pathways, ammonia is converted to urea and glutamine thereby leading to a reduction in ammonia levels in patients with hepatic encephalopathy. LOLA also has direct hepatoprotective effect through the synthesis of the antioxidant glutathione (GSH) from l-ornithine during transamination to glutamate. Increased production of nitric oxide (NO) from l-arginine in the urea cycle increases hepatic microcirculation. This ammonia lowering property of LOLA in hepatic encephalopathy due to cirrhosis, acute liver failure has been demonstrated in randomized clinical trials.

Source: Kircheis G, et al. Drugs. 2019 Feb;79(1):23-29.