EFFECTS OF ORNITHINE ASPARTATE ON PLASMA AMMONIA AND PLASMA AMINO-ACIDS IN PATIENTS WITH CIRRHOSIS - A DOUBLE-BLIND, RANDOMIZED STUDY USINGA 4-FOLD CROSSOVER DESIGN

This paper documents dose-dependent effects of ornithine aspartate (OA ) on postprandial hyperammonemia and plasma amino acids. Ten patients with cirrhosis were randomized to undergo 1 out of 4 infusion series. Each series consisted of four 8-h infusions (09:00 h-17:00 h), with pl acebo (NaCl), 5 g, 20 g or 40 g of OA being administered on separate d ays in varying sequences. This 4-fold crossover design was double-blin d. On infusion days, patients received 2 oral protein loads (0.25 g/kg at 09:00 h and 0.5 g/kg at 13:00 h). Venous blood samples were drawn every 2 h and the 24-h urine was collected. In addition to measuring p lasma ammonia and amino acids, the urea production rate, serum glucose and serum insulin were analyzed. A significant postprandial rise in t he ammonia concentration was noted during the infusions of placebo and 5 g of OA but did not occur with the dosages of 20 g (after the secon d protein load) and 40 g (after both protein loads). Furthermore, the latter dose, compared with placebo, significantly reduced plasma ammon ia after the minor protein load. Urea production rate increased when 2 0 g or 40 g of OA was administered. Of the amino acids involved in the metabolic pathways of ornithine and/or aspartate, glutamate showed a rise in its plasma level following infusion of 40 g of OA, whereas glu tamine did not. Concentrations of methionine, phenylalanine, tyrosine, threonine, serine and glycine declined progressively with increasing doses of OA (5-40 g). The highest dose of the drug caused hyperglycemi a and hyperinsulinemia. We conclude that 40 g of OA/8 h are necessary if postprandial hyperammonemia is to be counteracted. The promotion of urea synthesis does not necessarily contribute to the reduction of pl asma ammonia, since it can be accounted for by the nitrogen load in th e form of OA. Whether or not the increased availability of OA-derived glutamate intensifies hepatic and/or peripheral glutamine formation re mains to be clarified. There are studies which support the hypothesis that the decrease in the plasma concentrations of amino acids not clos ely related to OA can be ascribed, in part, to reduced amino acid outp ut from peripheral tissues.