Disposition of Salicylic Acid in Malnourished Ethiopian Children after Single Oral Dose

Abstract

The disposition of salicylic acid and salicyluric acid was studied in 57 Ethiopian children of varying nutritional status after oral administration of sodium salicylate in single doses of either 12.5 or 25 mg/kg. There was no apparent influence of nutritional status on oral salicylate disposition when related to total plasma concentrations. Unbound concentrations were predicted from total plasma concentrations on the basis of a single time point determination of protein binding in each individual, according to a Scatchard model. Areas under the unbound plasma concentration-time curve were larger and the fractional excretion of salicyluric acid was lower in children with kwashiorkor compared with control individuals. This was interpreted as lower hepatocellular metabolic activity in patients with kwashiorkor. Children with marasmus retained an unimpaired capacity for salicylate metabolism. The influence of saturable distribution and elimination are discussed.

Influence of nutritional status on the pharmacokinetics of acetylsalicylic acid and its metabolites in children with autoimmune disease

“…A lower intrinsic clearance in kwashiorkor patients was indicated by greater AUC values for the unbound drug. The observed difference in fractional salicyl glucuronide excretion in kwashiorkor patients reflects a diminished formation of SUA and is not an indication of metabolic capacity for salicylate glucuronidation (25). Salicylic acid is eliminated from the body by biotransformation to SUA, salicyl acyl and phenolic glucuronides, and GA and by renal excretion of unmetabolized drug.…”

“…A study of the disposition of SA in 57 malnourished Ethiopian children after administration of either a high or low single oral dose showed that the plasma half-lives and predicted half-lives of the unbound drug after the high dose were slightly longer in NUTRITIONAL STATUS AND SALICYLATES IN CHILDREN 321 the kwashiorkor group than in the control group, whereas the reverse was true after the low dose (both P ≤ 0.05) (25). The AUC of SUA did not differ significantly with nutritional status or increment of dose.…”