Depletion of Plasma Glycine and Effect of Glycine by Mouth on Salicylate Metabolism During Aspirin Overdose

Abstract

<jats:p> 1 The metabolism of aspirin was investigated in 45 patients who had taken self-administered overdose of aspirin and were treated with fluids only, glycine, N-glycylglycine by mouth, or by sodium bicarbonate i.v. </jats:p><jats:p> 2 The major metabolite recovered in the urine of patients treated with oral fluids, glycine or N-glycylglycine was salicyluric acid, which accounted for means of 51%, 47% and 38% of the total, respectively; salicylic acid comprised 19%, 29% and 29%. In contrast, salicylic acid (42%) was the major urinary metabolite recovered from patients treated with sodium bicarbonate. </jats:p><jats:p> 3 Plasma glycine concentrations in healthy volunteers who had taken no aspirin remained constant through the day and were not affected by a therapeutic dose (500 mg) of aspirin. Plasma glycine was consistently lower in patients with aspirin overdose than in these healthy volunteers, suggesting depletion of available glycine. </jats:p><jats:p> 4 Orally administered glycine and N-glycylglycine increased plasma glycine. While the fraction of total salicylate recovered as salicyluric acid was not altered, the maximum rate of excretion of salicyluric acid was higher in patients who received glycine than in the control group; there was no significant difference in the maximum rate of excretion of salicyluric acid between the group that received glycine and the group that received N-glycylglycine. 5 The data suggest that exogenous glycine increases the rate of formation of salicyluric acid in salicylate overdose. </jats:p>

The glycine deportation system and its pharmacological consequences

“…Healthy volunteers who took a single 500 mg tablet of aspirin had intermediate values of 12.8±0.5 mg/l (171 ±7 µM) (Patel et al, 1990). Aspirin administration, in particular aspirin overdose, causes GLY deportation, presumably via the renal mitochondrial system.…”

A Reassessment of the Treatment of Salicylate Poisoning

“…In the glycine treated patients, plasma glycine (which was initially below the normal range) increased, and salicyluric acid reestablished itself as the major urinary metabolite. Salicylic acid was the major metabolite in the bicarbonate and oral fluid treated groups (Patel et al 1990b). The maximum rate of excretion of salicyluric acid (a close approximation to its rate of formation) was significantly higher in the glycine recipients than in those treated with oral fluids, and higher than those treated by alkalinisation.…”