Utilization of intravenously administered N-acetyl- l-glutamine in humans

Abstract

l-glutamine is too unstable for inclusion in solutions for parenteral nutrition, but its acetylated analogue, N-acetyl- l-glutamine is not. The purpose of this three-part study was to investigate the utilization of intravenously (IV) administered acetylglutamine in humans. In study 1, nine healthy postabsorptive subjects were given 9.4 g acetylglutamine IV during four hours. In study 2, five healthy subjects were studied on two occasions following an overnight fast. They were given 9.4 g of acetylglutamine or an equivalent amount of glutamine as part of a total parenteral nutrition (TPN) regimen during 7.2 hours. A control group of five subjects was given the same TPN regimen, but without acetylglutamine or glutamine. The nutrient solution included glucose, amino acids, and a fat emulsion, supplying 9.4 g nitrogen and 6,300 kJ in a total volume of 1.8 L. In study 3, four patients were studied the day after major surgery. They were given the same TPN regimen as in study 2, containing 9.4 g acetylglutamine, during 7.2 hours. Plasma concentrations and urinary excretion of acetylglutamine and glutamine were measured in all three studies, and so were splanchnic and renal exchange of acetylglutamine and glutamine in study 1. In study 1, the plasma concentration of glutamine rose from 594 ± 28 μmol/L to 728 ± 26 μmol/L ( P < .001), whereas plasma levels of acetylglutamine exceeded 1,000 μmol/L in all subjects at the end of infusion. The eight-hour urinary excretion of acetylglutamine and glutamine corresponded to 18% of the infused amount of acetylglutamine. No net exchange of acetylglutamine across the splanchnic tissues could be determined, but the kidneys extracted acetylglutamine (165 ± 54 μmol/min) and there was a glutamine release (90 ± 10 μmol/min). In study 2, glutamine concentration rose from 537 ± 42 μmol/L to 726 ± 51 μmol/L ( P < .001) when acetylglutamine was infused and from 609 ± 25 μmol/L to 809 ± 42 μmol/L ( P < .001) with glutamine administration. No significant increase in glutamine concentration was found in the control study. Urinary excretion of acetylglutamine and glutamine over 24 hours corresponded to 34% of the administered acetylglutamine dose. In study 3, glutamine concentration was 422 ± 33 μmol/L before infusion and 495 ± 46 μmol/L at the end (ns). Acetylglutamine concentration rose from undetectable values to 517 ± 84 μmol/L. Urinary excretion of acetylglutamine and glutamine during 24 hours corresponded to 41% of the infused amount. The present findings demonstrate that acetylglutamine infusion is accompanied by a rise in arterial glutamine levels after deacetylation of acetylglutamine, primarily in the kidneys. However, 20% to 40% of the administered dose is excreted in urine, rendering acetylglutamine a possible but not ideal glutamine precursor for clinical use.