Source: Marketing Authorisation Holder Publisher: Merz Pharmaceuticals GmbH, Eckenheimer Landstr. 100, 60318 Frankfurt am Main, Germany
Pharmacotherapeutic group: Liver therapy
ATC code: A05BA
In vivo, L-ornithine L-aspartate acts on two key ammonia detoxification pathways urea synthesis and glutamine synthesis via the amino acids ornithine and aspartate.
Urea synthesis takes place in the periportal hepatocytes, in which ornithine serves both as an activator of the two enzymes ornithine carbamoyl transferase and carbamoyl phosphate synthetase and as a substrate for urea synthesis.
Glutamine synthesis is localised in the perivenous hepatocytes. Under pathological conditions in particular, aspartate and other dicarboxylates including metabolic products of ornithine are taken up into the cells where they are used in the form of glutamine to bind ammonia.
Both physiologically and pathophysiologically glutamate serves as an ammonia-binding amino acid. The resulting amino acid glutamine not only provides a non-toxic form for the excretion of ammonia but also activates the important urea cycle (intercellular glutamine exchange).
Under physiological conditions ornithine and aspartate are not limiting for urea synthesis.
Experimental studies in animals point to increased glutamine synthesis as a mechanism of the ammonia-lowering effect. Some clinical studies have shown an improvement in the ratio of branchedchain to aromatic amino acids.
Ornithine and aspartate have a short elimination half-life of 0.3–0.4 hours. Some of the aspartate is excreted unchanged in the urine.
Based on pharmacological safety studies, preclinical data show that with correct use there is no particular risk of toxicity following repeated administration or mutagenicity in humans.
No studies on carcinogenic potential have been carried out.
In a dose discovery study, L-ornithine L-aspartate was investigated for reproduction toxicity only to a limited extent.
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