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.
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 placebo (NaCl), 5 g, 20 g or 40 g of OA being administered on separate days in varying sequences. This 4-fold crossover design was double-blind. 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 plasma ammonia and amino acids, the urea production rate, serum glucose and serum insulin were analyzed. A significant postprandial rise in the 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 second protein load) and 40 g (after both protein loads). Furthermore, the latter dose, compared with placebo, significantly reduced plasma ammonia after the minor protein load. Urea production rate increased when 20 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 glutamine 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 hyperglycemia and hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Staedt
U
U
Department of Pathophysiology, Medical Clinic I, University of Heidelberg, Mannheim, Germany.
Leweling
H
H
Gladisch
R
R
Kortsik
C
C
Hagmüller
E
E
Holm
E
E
D000328:Adult; D000596:Amino Acids / Q000097:blood*; D000641:Ammonia / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014508:Urea / Q000097:blood
D000596:Amino Acids; D001786:Blood Glucose; D004151:Dipeptides; D007328:Insulin; D000641:Ammonia; D014508:Urea; C002939:ornithylaspartate