Protein Binding of Salicylic and Salicyluric Acid in Serum from Malnourished Children: The Influence of Albumin, Competitive Binding and Non-esterified Fatty Acids

Abstract

The serum protein binding of salicylic and salicyluric acid has been determined by ultrafiltration in 60 children after administration of oral salicylate. The children were classified according to nutritional status: well-nourished (n = 12), underweight (n = 12), marasmic (n = 17) marasmic-kwashiorkor (n = 7) and kwashiorkor (n = 12). Salicylic acid free fractions were 0.106 +/- 0.026, 0.114 +/- 0.069, 0.141 +/- 0.037, 0.285 +/- 0.279 and 0.438 +/- 0.190 in the five groups, respectively. Salicyluric acid free fractions were 0.184 +/- 0.057, 0.280 +/- 0.282, 0.236 +/- 0.114, 0.484 +/- 0.497 and 0.646 +/- 0.261, respectively. The degree of binding was dependent on serum albumin levels, ligand concentrations and non-esterified fatty acids (NEFA). The NEFA/albumin ratio ranged from 0.05 to 6.6. The fitting of a one-site Scatchard binding model to the collective data was improved when a decrease was allowed for in the number of binding sites in proportion to NEFA concentrations. Salicyluric acid binding could be fitted only when inhibition of the parent compound was included. Binding was not affected by age or sex. The major determinants of salicylate binding in sera from malnourished children have thus been identified.

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

“…We have previously reported elevated salicylic acid and salicyluric acid unbound fractions in the kwashiorkor subgroup of the present study population (Ashton et al 1989). The degree of protein binding is dependent on ligand concentrations, with each individual exhibiting an apparent variation with time after dose.…”

“…The binding of salicylic acid to albumin is saturable at therapeutic drug concentrations, leading to a concentration-(or dose-) dependent volume of distribution (Levy & Yaffe 1974). We have previously reported a significant decrease in salicylic acid and salicyluric acid serum protein binding in the kwashiorkor subgroup of the present study population (Ashton et al 1989). Pharmacokinet.…”

“…Instead, unbound concentrations were extrapolated from a single sample in each patient according to a model previously described (Ashton et al 1989). Instead, unbound concentrations were extrapolated from a single sample in each patient according to a model previously described (Ashton et al 1989).…”

The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-infected Children in Tororo, Uganda

“…Mechanistically, malnutrition may reduce albumin or α-acid glycoprotein concentrations, 62,63 thereby increasing the free fraction of highly protein bound drugs such as LPV and EFV thus enhancing drug metabolism and elimination. High NVP exposures may also be explained by diminished auto-induction of NVP metabolism 64,65 due to malnutrition.…”

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

“…Serum protein binding values of Ϸ57% were found in both groups at the highest doses, despite significantly lower serum albumin concentrations in the undernourished group (23). A significant decrease in serum protein binding of SA and SUA in a kwashiorkor subgroup was found by Ashton et al (24). No effect of nutritional status on plasma salicylate concentrations was observed after oral administration of aspirin in a small study of African children (23).…”