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Title: Metabolism of aspirin after therapeutic and toxic doses
Author: Patel, Dipak Kumar Vallabhdas
ISNI:       0000 0001 3475 4175
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 1985
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The metabolism of aspirin has been investigated in man following a therapeutic (600 mg) dose and after overdose. The major urinary metabolite in volunteers after the therapeutic dose was salicyluric acid and a sex-related difference in its excretion and that of salicylic acid was observed. Capacity limited formation of salicyluric acid has been demonstrated for the first time in a substantial number of paients with aspirin overdose. Urinary excretion of gentisic acid, salicylic acid and salicyl phenolic glucuronide was higher in overdose patients compared with the volunteers. In addition, the urinary excretion rates of aspirin metabolites and in particular salicyluric acid and salicyl phenolic glucuronide in individual patients varied with time after admission and the maximum observed rates were often greatly in excess of those previously reported in the literature. Depletion of plasma glycine also occurred after aspirin overdose. The in vivo plasma glycine pool was enriched by oral administration of glycine or N-glycylglycine. Glycine and N-glycylglycine treatments were as effective as the standard urine alkalinisation regimen in enhancing renal excretion of total salicylate after overdose but the mechanism of this action is unclear. Thus exogenous glycine may be of therapeutic value in salicylate overdose. The metabolism of 14c-aspirin was also studied in rats over a ten fold dose range and was found to be dose dependent. The principal urinary metabolite after each dose was salicylic acid and salicyluric acid formation was capacity limited. Oral administration of glycine concurrently with aspirin increases the urinary excretion of salicyluric acid. Gentisuric acid and salicyluric phenolic glucuronide have also been quantified in man and rat urine. Metabolism of aspirin was found to be similar in man and rat, although there were quantitative differences; thus rat may serve as a useful experimental model to study man.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Aspirin metabolism