SpringerLink
Log in

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

  • Original Research Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alleyne GAO. Cardiac function in severely malnourished Jamaican children. Clinical Science 30: 553–562, 1966

    PubMed  CAS  Google Scholar 

  • Alleyne GAO. The effect of severe protein calorie malnutrition on the renal function of Jamaican children. Paediatrics 39: 400–411, 1967

    CAS  Google Scholar 

  • Ashton M, Bolme P, Zerihun G. Protein binding of salicylic and salicyluric acid in serum from malnourished children: the influence of albumin, competitive binding and non-esterified fatty acids. Journal of Pharmacy and Pharmacology 41: 474–480, 1989

    Article  PubMed  CAS  Google Scholar 

  • Bochner F, Graham GG, Polverino A, Imhoff DM, Tregenza RA, et al. Salicyl phenolic glucuronide pharmacokinetics in patients with rheumatoid arthritis. European Journal of Clinical Pharmacology 32: 153–158, 1987

    Article  PubMed  CAS  Google Scholar 

  • Bravo ME, Jarpa S, Monckeberg F, Pizarro G. Cinética de niveles plasmaticos de salicilato en niños desnutridos. Revista Chilena de Pediatria 49: 45–50, 1978

    PubMed  CAS  Google Scholar 

  • Brooks SE, Goldon MH, Taylor E. Hepatic ultra-structure in children with protein-energy malnutrition. West Indian Medical Journal 41: 139–145, 1992

    PubMed  CAS  Google Scholar 

  • Chatterjee KK, Mukherjee KL. Phospholipids of the liver in children suffering from protein-calorie undernutrition. British Journal of Nutrition 22: 145–151, 1968

    Article  PubMed  CAS  Google Scholar 

  • Editorial. Classification of infantile malnutrition. Lancet 2: 302–303, 1970

  • Furst DE, Tozer TN, Melmon KL. Salicylate clearance, the resultant of protein binding and metabolism. Clinical Pharmacology and Therapeutics 26: 380–389, 1979

    PubMed  CAS  Google Scholar 

  • Gibson T, Zaphiropoulos G, Grove J, Widdop B, Berry D. Kinetics of salicylate metabolism. British Journal of Clinical Pharmacology 2: 233–238, 1975

    Article  PubMed  CAS  Google Scholar 

  • Graham GG, Champion CD, Day RO, Pauli PD. Patterns of plasma concentrations and urinary excretion of salicylate in rheumatoid arthritis. Clinical Pharmacology and Therapeutics 22: 410–420, 1977

    PubMed  CAS  Google Scholar 

  • Ho PC, Triggs EJ, Bourne DWA. The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites. British Journal of Clinical Pharmacology 19: 675–684, 1989

    Article  Google Scholar 

  • Hutt AJ, Caldwell J, Smith RL. The metabolism of [carboxyl-14C]aspirin in man. Xenobiotica 12: 601–610, 1982

    Article  PubMed  CAS  Google Scholar 

  • Komiya I. Urine flow dependence of renal clearance and interrelation of renal reabsorption and physicochemical properties of drugs. Drug Metabolism and Disposition 14: 239–245, 1986

    PubMed  CAS  Google Scholar 

  • Levy G. Pharmacokinetics of salicylate in man. Drug Metabolism Reviews 9: 3–19, 1979

    Article  PubMed  CAS  Google Scholar 

  • Levy G, Tsuchiya T, Amsel LP. Limited capacity for salicyl phenolic glucuronide formation and its effect on the kinetics of salicylate elimination in man. Clinical Pharmacology and Therapeutics 13: 258–268, 1972

    PubMed  CAS  Google Scholar 

  • Levy G, Yaffe SJ. Relationship between dose and apparent volume of distribution of salicylate in children. Paediatrics 54: 713–717, 1974

    CAS  Google Scholar 

  • Miaskiewicz SL, Shively CA, Vesell ES. Sex differences in absorption of kinetics of sodium salicylate. Clinical Pharmacology and Therapeutics 31: 30–37, 1982

    Article  PubMed  CAS  Google Scholar 

  • Montgomery PR, Berger LG, Mitenko PA, Sitar DS. Salicylate metabolism: effects of age and sex in adults. Clinical Pharmacology and Therapeutics 39: 571–576, 1986

    Article  PubMed  CAS  Google Scholar 

  • Montgomery PR, Sitar DS. Acetylsalicylic acid metabolites in blood and urine after plain and enteric-coated tablets. Biopharmaceutics and Drug Disposition 7: 21–25, 1986

    Article  CAS  Google Scholar 

  • Øie S, Tozer TN. Effect of altered plasma protein binding on apparent volume of distribution. Journal of Pharmaceutical Sciences 68: 1203–1205, 1979

    Article  PubMed  Google Scholar 

  • Rubin GM, Tozer TN, Øie S. Concentration-dependence of salicylate distribution. Journal of Pharmacy and Pharmacology 35: 115–117, 1983

    Article  PubMed  CAS  Google Scholar 

  • Schachter D, Manis JG. Salicylate and salicyl conjugates: fluorimetric estimation, biosynthesis and renal excretion in man. Journal of Clinical Investigation 37: 800–807, 1958

    Article  PubMed  CAS  Google Scholar 

  • Shastri RA. Steady-state kinetics of salicylic acid in undernutrition. World Review of Nutrition and Dietetics 43: 192–197, 1984

    PubMed  CAS  Google Scholar 

  • Tandon BN, Ramanujan RA, Tandon HD, Gandhi PC. Liver injury in protein calorie malnutrition: an electron microscopic study. American Journal of Clinical Nutrition 27: 550–558, 1974

    PubMed  CAS  Google Scholar 

  • Thabrew MI, Olorunsogo OO, Olowookere JO, Bababunmi EA. Possible defect in xenobiotic activation before glycine conjugation in protein-energy malnutrition. Xenobiotica 12: 849–853, 1982

    Article  PubMed  CAS  Google Scholar 

  • Treluyer JM, Sultan E, Alexandre JA, Roux A, Flouvat B, et al. Pharmacocinetique de l’aspirine chez l’enfant africain normonutri et malnutri. Archives Francaises de Pediatrie 48: 337–341, 1991

    PubMed  CAS  Google Scholar 

  • Varma DR, Yue TL. Influence of age, sex, pregnancy and protein-calorie malnutrition on the pharmacokinetics of salicylate in rats. British Journal of Pharmacology 82: 241–248, 1984

    Article  PubMed  CAS  Google Scholar 

  • Wilson JT, Howell RL, Holladay MW, Brills GM, Chrastil J, et al. Gentisuric acid: metabolic formation in animals and identification as a metabolite of aspirin in man. Clinical Pharmacology and Therapeutics 23: 635–643, 1978

    PubMed  CAS  Google Scholar 

  • Yue TL, Varma DR. Pharmacokinetics, metabolism and disposition of salicylate in protein-deficient rats. Drug Metabolism and Disposition 10: 147–152, 1982

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biopharmaceutics and Pharmacokinetics, Uppsala University, Uppsala, Sweden

    Michael Ashton & Lennart K. Paalzow

  2. Department of Paediatrics, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden

    Per Bolme & Kirsten Holmberg

  3. Department of Pediatrics and Child Health, Addis Ababa University, Ethio-Swedish Children’s Hospital, Addis Ababa, Ethiopia

    Getnet Zerihun

Authors
  1. Michael Ashton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Per Bolme
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Getnet Zerihun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kirsten Holmberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lennart K. Paalzow
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ashton, M., Bolme, P., Zerihun, G. et al. Disposition of Salicylic Acid in Malnourished Ethiopian Children after Single Oral Dose. Clin. Pharmacokinet. 25, 483–494 (1993). https://doi.org/10.2165/00003088-199325060-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199325060-00006

Keywords

Search

Navigation