Hepa-Merz Mechanism of Action

Pharmacotherapeutic group: Liver therapy. ATC code: A05BA.
Pharmacology: Pharmacodynamics: Granules: In vivo, L-Ornithine-L-Aspartate exerts its effects through the amino acids, ornithine and aspartate, via two key methods of ammonia detoxification: urea synthesis and glutamine synthesis.
Urea synthesis takes place in the periportal hepatocytes. In these cells, ornithine serves both as an activator of the enzymes ornithine-carbamoyltransferase and carbamoyl phosphate synthetase and also as the substrate of urea synthesis.
Glutamine synthesis is localized in the perivenous hepatocytes. Particularly under pathological conditions, aspartate and other dicarboxylates, including the metabolic products of ornithine, are absorbed into the cells and used there to bind ammonia in the form of glutamine.
Glutamate is an amino acid that binds ammonia under both physiological and pathophysiological conditions. The resulting amino acid glutamine not only represents 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.
Animal studies suggest that the ammonia-reducing effect of L-Ornithine-L-Aspartate is caused by enhanced glutamine synthesis. Individual clinical studies have shown an improved branched-chain amino acid/aromatic amino acid quotient.
Infusion: 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 localized in the perivenous hepatocytes. Under pathological conditions in particular, aspartate and other dicarboxylates - including metabolic products of ornithine - are taken up into 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 branched-chain to aromatic acids.
Pharmacokinetics: Granules: L-Ornithine-L-Aspartate is rapidly absorbed and cleaved to form ornithine and aspartate.
Both amino acids have a short elimination half-life of 0.3-0.4 hours. A fraction of the aspartate is recovered in unmetabolised form in the urine.
Infusion: 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.
Toxicology: Preclinical safety data: Granules: Preclinical data, based on safety pharmacological studies and chronic toxicity and mutagenicity studies, do not suggest any particular risk to humans following correct administration.
No studies into any carcinogenic potential have been performed.
In a dose-finding study, L-Ornithine-L-Aspartate was insufficiently investigated in terms of its toxicity in relation to reproduction.
Infusion: 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.