Kinetics of salicylate metabolism.

Abstract

1Nine patients with rheumatoid arthritis or non-inflammatory backache were given soluble aspirin (65 mg/kg body weight) daily. There was no significant difference between the plasma salicylate of those with rheumatoid arthritis and those with backache. 2 Two patients had plasma salicylate values that differed significantly from the remainder but neither these results nor the marginal differences between plasma salicylate levels of the others could be explained by individual variations in the capacity for excreting salicyluric acid or salicyl phenolic glucuronide. 3 Increasing the dose of aspirin in four patients demonstrated the reduced proportions of salicyluric acid and salicyl phenolic glucuronide excreted at high doses and the increased importance of unchanged salicylic acid as an excretory pathway. These findings are consistent with a limiting capacity for salicyluric acid and salicyl phenolic glucuronide synthesis and excretion. 4 The findings in one patient suggested that inter-subject variations in the capacity for producing salicyl phenolic glucuronide and salicyluric acid may have an effect on plasma salicylate levels at high doses of aspirin.

Value of monitoring plasma salicylate levels in treating juvenile rheumatoid arthritis. Observations in 42 cases.

“…There is a clear correlation between plasma salicylate concentration and the urinary excretion of free salicylate, but not of salicyluric acid or total metabolites. These observations agree with those of Gibson et al (1975). Simultaneous administration of steroids increases the urinary excretion of free salicylate, salicyluric acid, and total metabolites, expressed as a percentage of excretion related to the salicylate dose (Fig.…”

“…This could be caused by variations in urinary pH (MacPherson et al, 1955), although in our cases the pH of the urine only ranged between 5 and 6. We interpret our results, obtained on the 24hour urines of 7 children, as confirming the limited capacity of the liver to conjugate salicylate with glycine, which is likely to be the first process to be saturated (Levy, 1968;Gibson et al, 1975).…”

Metabolism of salicylate during chronic aspirin therapy.

“…They attributed this effect to poor subject compliance. In other studies where plasma salicylate levels were monitored for longer than 7 days, this decline may not have been observed due to dosage changes during the particular study (Gibson, Zaphiropoulos, Grove, Widdop & Berry, 1975;Paulus, Seigel, Mongan, Okin & Calabro, 1971). We have observed, in the treatment of certain patients undergoing chronic aspirin therapy, the development of an apparent tolerance to aspirin.…”

AML1-ETO mediates hematopoietic self-renewal and leukemogenesis through a COX/β-catenin signaling pathway

“…Both doses are within the clinically achievable plasma concentrations in human. 30,31 The cell growth percentages in the presence of these drugs were determined as compared with the corresponding DMSO-treated samples. We found that at least 1 of the 2 drugs caused more than 50% of reduction in the growth of 5 of 6 AML samples tested without affecting the growth of human CD34 1 cells ( Figure 7C).…”