Ornithine-aspartate

As early as 1932, H.A. Krebs and K. Henseleit established that of the investigated amino acids, only ornithine was able to effect a real increase in the synthesis of urea from ammonia (although arginine also displayed low efficacy), (quot. 57) Thus it seemed possible to raise the turnover of ammonia in the metabolism process by using intermediates of the urea cycle. (127) (s. tab. 15.6) (s. fig. 3.10) To this end, ornithine aspartate (oral and parenteral route), arginine malic... 

A daily dosage of 0.3 g/kg BW is recommended (approx. 3 X 10 g). The use of BCAA has become established for latent and manifest HE. It has even been possible to render patients fit to drive again. No side effects are known. The efficacy of branched-chain amino acids as parenteral i.v. therapy is well validated for the severe stages II—IV of HE. The concomitant intake of arginine and ornithine aspartate has proved to be particularly effective. (127) Eatty emulsions are to be avoided since they release tryptophan from the albumin binding and inhibit the utilization of branched-chain amino acids in the musculature. (123, 126, 129, 131, 133, 138, 140, 145, 148-151, 170) (s. p. 860)... 

Ornithine aspartate (40 g/8 hours as intravenous infusion) (51) and flumazenil are advisable for the treatment of hepatic precoma and coma. 

The above-mentioned measures do not combat the cause(s) or eliminate the primary pathogenetic reactions (with a few exceptions). The general aim is to prevent progression of the disease, ideally until the cirrhosis comes to a halt. When such medication is administered effectively, complicative developments can also be prevented. Pathogenetic primary reactions often initiate a cascade of secondary mechanisms, in particular of a biochemical nature. This is true, for example, of the inhibition of concomitant cholestasis during the course of cirrhosis by ursodeoxycholic acid (97), the reduction in lipid peroxidation by silymarin, the inhibition of fibrogenesis by colchicine (82) or silymarin (sometimes with improved quality of life), and the elimination of hyperammonaemia by ornithine aspartate. (145) (s. p. 279)... 

There are several biochemical and clinical modes of action associated with ornithine aspartate, (s. tab. 40.11)... 

The various modes of action provide the basis for the following therapeutic indications of ornithine aspartate ... 

Latent encephalopathy, detectable by psychometric tests (s. p. 202), is frequent experience has shown that it can rapidly become manifest. Of the urea-cycle amino acids suitable for therapy, ornithine aspartate has proved the most successful - also as an i.v. infusion in the postoperative phase, (s. pp 279, 733)... 

Staedt, LL, Lewellng, H., Gladisch, R., Kortsick, C., Hagmiiller, E., Holm, E. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J. Hepatol. 1993 19 424-430... 

See also Urea Cycle, Amino Acids Not In Proteins, Ornithine, Aspartate... 

Ammonia metabolism within the muscle may be improved by the administration of L-omithine-L- aspartate (LOLA). Controlled trials suggest that enteral and parenteral formulations of ornithine aspartate significantly reduce blood ammonia levels and have useful therapeutic effects in patients with cirrhosis and encephalopathy (Kircheis et al., 1997 Stauch et al., 1998). Poo et al. (2006) recently showed in a randomized, lactulose-controlled study of oral ornithine-aspartate in 20 patients with clinically overt HE that LOLA in contrast to lactulose significantly improved parameters of mental status, number connection test scores, asterixis scores and EEG. Both lactulose and LOLA reduced serum ammonia levels and improved quaUty of life scores. Since only 20 patients were included in this study the results cannot be considered proof for the superiority of LOLA compared to lactulose, while the data underscore the effect of both agents. Ornithine aspartate is well tolerated in general. From a theoretical point of view the combination of disaccharides and ornithine aspartate may be useful in patients with insufficient efficacy of only one of the two drugs. 

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