Metabolism of aspirin after therapeutic and toxic doses.

Abstract:

:1 The urinary recovery of metabolites of aspirin (ASA) was studied in 45 volunteers who took a therapeutic dose (600 mg) of ASA by mouth and in 37 patients who took ASA in overdose. 2 The main metabolite recovered from the volunteers was the glycine conjugate, salicyluric acid (SUA), which accounted for 75.01 +/- 1.19% of total urinary metabolites, whereas salicylic acid (SA) accounted for 8.82 +/- 0.56%. Recovery of SUA was negatively correlated with that of SA (r = -0.8625, P less than 0.001). 3. In 24 patients with admission plasma salicylate concentrations of 240-360 mg l-1, SUA accounted for 46.66 +/- 3.22% and SA for 31.88 +/- 4.02%. 4. In 13 patients with admission plasma salicylate concentrations of 715-870 mg l-1, SUA accounted for 21.57 +/- 3.65% and SA for 64.72 +/- 4.82%. 5. Reduced excretion of salicylate as SUA was also accompanied by increased elimination as gentisic acid and salicylic acid phenolic glucuronide indicating that the unsaturated processes that lead to the formation of these metabolites contribute significantly (22-23%) to the inactivation of large doses of salicylate. 6. While the Michalis-Menten kinetics of ASA have been well demonstrated at lower doses, our findings illustrate the progressive saturation of SUA formation under conditions of increasing ASA load to toxic amounts and raise issues about the in-vivo glycine pool when ASA is taken in overdose.

journal_name

Hum Exp Toxicol

authors

Patel DK,Hesse A,Ogunbona A,Notarianni LJ,Bennett PN

doi

10.1177/096032719000900302

subject

Has Abstract

pub_date

1990-05-01 00:00:00

pages

131-6

issue

3

eissn

0960-3271

issn

1477-0903

journal_volume

9

pub_type

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