salicylates and Protein-Energy-Malnutrition

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.

Topics: Administration, Oral; Child, Preschool; Ethiopia; Female; Hippurates; Humans; Infant; Kidney; Male; Protein-Energy Malnutrition; Salicylates; Salicylic Acid

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.

Topics: Binding, Competitive; Blood Proteins; Child, Preschool; Chromatography, High Pressure Liquid; Fatty Acids, Nonesterified; Female; Hippurates; Humans; Kwashiorkor; Male; Nutrition Disorders; Protein Binding; Protein-Energy Malnutrition; Salicylates; Salicylic Acid; Serum Albumin

The influence of age, sex, pregnancy and protein-calorie malnutrition (PCM) on the plasma t1/2, plasma clearance (Clp) and apparent volume of distribution (Vd) of sodium salicylate (62 mumol kg-1) was determined in Sprague-Dawley rats. Female and male rats of five different age groups (ages in weeks: pups 1, weanling 3, young 8-9, adult including pregnant 14-15, old 56-60) including three age groups with PCM (8-9, 14-15 and 56-60 weeks old) were used. Plasma and urinary salicylates were assayed by h.p.l.c. Plasma t1/2 was longer and Clp smaller in pups than in weanling and young rats and comparable to values for old rats; Vd of salicylate in pups was larger than in any other group of rats. Plasma t1/2 was longer and Clp as well as Vd of salicylate were smaller in adult females than in males of comparable age. Relative to nonpregnant adult females, Vd of salicylate in pregnant rats was larger but plasma t1/2 and Clp were unchanged. In all groups of rats studied, PCM decreased the plasma t1/2 and increased the Clp of salicylate; Vd was unchanged. Changes in salicylate pharmacokinetics were not due to any differences in serum protein-salicylate binding or to serum testosterone levels. Ovariectomy decreased the plasma t1/2 of salicylate but castration of male rats had no significant effect. Administration of testosterone to ovariectomized female rats exerted no significant effect on salicylate pharmacokinetics. It is concluded that the physiological state and the nutritional status can modify salicylate pharmacokinetics; in so far as the rat model reflects the human situation, these variables should be taken into account for a rational salicylate therapy.

Topics: Aging; Animals; Blood Proteins; Castration; Diet; Female; Kinetics; Male; Pregnancy; Pregnancy, Animal; Protein Binding; Protein-Energy Malnutrition; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Sex Characteristics; Testosterone