Depletion of plasma glycine and effect of glycine by mouth on salicylate metabolism during aspirin overdose.

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. 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. 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. 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.