Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Nov;54(5):1221–1226. doi: 10.1172/JCI107865

Kinetics of Salicylate Elimination by Anephric Patients

David T Lowenthal 1,2, William A Briggs 1,2, Gerhard Levy 1,2
PMCID: PMC301669  PMID: 4424666

Abstract

The objectives of this research were to determine the kinetics of salicylate elimination in anephric patients and particularly to establish if these patients form the major metabolite of salicylic acid, salicyluric acid, at a normal rate. This investigation was initiated because of conflicting reports concerning the contribution of the kidneys to the formation of salicyluric acid in man. Six patients, 20-44 yr old, three of whom were anatomically anephric while the other three were physiologically anephric, received an intravenous injection of 500 mg salicylic acid (as sodium salicylate)/1.73 m2 body surface area on an interdialysis day. Serial blood samples were obtained for 12 or 16 h after injection and the plasma was assayed for salicylic acid, salicyluric acid, total protein, albumin, and creatinine. Detailed pharmacokinetic analysis based on an open, two-compartment linear model revealed no significant differences in apparent volume of distribution and apparent first-order distribution and elimination rate constants between the anephric patients and normal adult subjects. An estimate of salicyluric acid formation rate by the anephric patients, based on the initial rate of increase of salicylurate concentrations in plasma, indicates that the metabolite is formed at a normal rate. These results suggest that the kidneys do not contribute significantly to the formation of salicyluric acid from salicylic acid in man.

Full text

PDF
1221

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andreasen F. Protein binding of drugs in plasma from patients with acute renal failure. Acta Pharmacol Toxicol (Copenh) 1973;32(6):417–429. doi: 10.1111/j.1600-0773.1973.tb01488.x. [DOI] [PubMed] [Google Scholar]
  2. Campion D. S. Decreased drug binding by serum albumin during renal failure. Toxicol Appl Pharmacol. 1973 Jul;25(3):391–397. doi: 10.1016/0041-008x(73)90312-8. [DOI] [PubMed] [Google Scholar]
  3. Hollister L., Levy G. Some aspects of salicylate distribution and metabolism in man. J Pharm Sci. 1965 Aug;54(8):1126–1129. doi: 10.1002/jps.2600540806. [DOI] [PubMed] [Google Scholar]
  4. Kamath B. L., Levy G. Letter: Renal contribution to drug biotransformation. J Pharm Sci. 1974 Aug;63(8):1342–1343. doi: 10.1002/jps.2600630851. [DOI] [PubMed] [Google Scholar]
  5. LEONARDS J. R., LEVY G. ABSORPTION AND METABOLISM OF ASPIRIN ADMINISTERED IN ENTERIC-COATED TABLETS. JAMA. 1965 Jul 12;193:99–104. doi: 10.1001/jama.1965.03090020013004. [DOI] [PubMed] [Google Scholar]
  6. Levy G., Amsel L. P., Elliott H. C. Kinetics of salicyluric acid elimination in man. J Pharm Sci. 1969 Jul;58(7):827–829. doi: 10.1002/jps.2600580705. [DOI] [PubMed] [Google Scholar]
  7. Levy G. Pharmacokinetics of salicylate elimination in man. J Pharm Sci. 1965 Jul;54(7):959–967. doi: 10.1002/jps.2600540703. [DOI] [PubMed] [Google Scholar]
  8. Levy G., Tsuchiya T., Amsel L. P. Limited capacity for salicyl phenolic glucuronide formation and its effect on the kinetics of salicylate elimination in man. Clin Pharmacol Ther. 1972 Mar-Apr;13(2):258–268. doi: 10.1002/cpt1972132258. [DOI] [PubMed] [Google Scholar]
  9. Levy G., Tsuchiya T. Salicylate accumulation kinetics in man. N Engl J Med. 1972 Aug 31;287(9):430–432. doi: 10.1056/NEJM197208312870903. [DOI] [PubMed] [Google Scholar]
  10. Levy G., Vogel A. W., Amsel L. P. Capacity-limited salicylurate formation during prolonged administration of aspirin to healthy human subjects. J Pharm Sci. 1969 Apr;58(4):503–504. doi: 10.1002/jps.2600580432. [DOI] [PubMed] [Google Scholar]
  11. Nelson E., Hanano M., Levy G. Comparative pharmacokinetics of salicylate elimination in man and rats. J Pharmacol Exp Ther. 1966 Jul;153(1):159–166. [PubMed] [Google Scholar]
  12. Reidenberg M. M., Affrime M. Influence of disease on binding of drugs to plasma proteins. Ann N Y Acad Sci. 1973 Nov 26;226:115–126. doi: 10.1111/j.1749-6632.1973.tb20474.x. [DOI] [PubMed] [Google Scholar]
  13. SCHACHTER D., MANIS J. G. Salicylate and salicyl conjugates: fluorimetric estimation, biosynthesis and renal excretion in man. J Clin Invest. 1958 Jun;37(6):800–807. doi: 10.1172/JCI103667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Tsuchiya T., Levy G. Biotransformation of salicylic acid to its acyl and phenolic glucuronides in man. J Pharm Sci. 1972 May;61(5):800–801. doi: 10.1002/jps.2600610530. [DOI] [PubMed] [Google Scholar]
  15. WIEGAND R. G., SANDERS P. G. CALCULATION OF KINETIC CONSTANTS FROM BLOOD LEVELS OF DRUGS. J Pharmacol Exp Ther. 1964 Dec;146:271–275. [PubMed] [Google Scholar]
  16. von Lehmann B., Wan S. H., Riegelman S., Becker C. Renal contribution to overall metabolism of drugs. IV. Biotransformation of salicylic acid to salicyluric acid in man. J Pharm Sci. 1973 Sep;62(9):1483–1486. doi: 10.1002/jps.2600620920. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES