pmc logo image
Logo of brjclinpharmJournal URL: http://www.blackwellpublishing.com/journal.asp?ref=0306-5251
Journal List > Br J Clin Pharmacol > v.10(Suppl 2); 1980

Formats:
Br J Clin Pharmacol. 1980; 10(Suppl 2): 285S–290S.
PMCID: PMC1430201
Copyright notice
Clinical pharmacokinetics of salicylates
A reassessment
Gerhard Levy
Small right arrow pointing to: This article has been cited by other articles in PMC.
Abstract
1 Aspirin is partly hydrolyzed to salicylic acid during absorption. Absorbed aspirin is rapidly hydrolyzed systemically. Salicylic acid elimination kinetics are dependent on drug concentration due to the limited capacity of two major biotransformation pathways: formation of salicyluric acid and of salicylphenolic glucuronide.
2 The time courses of the various pharmacological effects of single doses of aspirin are not directly coincident with the plasma concentrations of either aspirin or salicylic acid but there is reasonably good evidence that the pharmacological effects are related to the concentration of aspirin, salicylic acid, or both.
3 Steady-state plasma salicylate concentrations increase more than proportionally with increasing daily dose; the time required to reach steady state increases with increasing daily dose. Dosage intervals of 8 or even 12 h are usually sufficient to maintain plasma salicylate concentrations in the anti-inflammatory concentration range. Monitoring of plasma salicylate concentrations in this range is facilitated by the relatively small drug concentration fluctuations during a dosing interval at steady-state.
4 Limited data suggest that the pharmacological activity of salicylate is produced by free (unbound) drug. As the plasma protein binding of salicylic acid is concentration-dependent and subject to pronounced interindividual differences, it is preferable, at least in principle, to monitor free rather than total concentrations of salicylate in plasma. Although salicylate concentration in saliva reflects the free rather than total salicylate concentration in plasma or serum, use of saliva for indirect monitoring of plasma salicylate concentrations seems to be impractical for technical reasons.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (900K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
 
icon of scanned page 285S
285S
icon of scanned page 286S
286S
icon of scanned page 287S
287S
icon of scanned page 288S
288S
icon of scanned page 289S
289S
icon of scanned page 290S
290S
 
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Aarons LJ, Bochner F, Rowland M. A chronic dose-ranging kinetic study of salicylate in man [proceedings]. Br J Pharmacol. 1977 Nov;61(3):456P–457P. [PubMed]
  • Bardare M, Cislaghi GU, Mandelli M, Sereni F. Value of monitoring plasma salicylate levels in treating juvenile rheumatoid arthritis. Observations in 42 cases. Arch Dis Child. 1978 May;53(5):381–385. [PubMed]
  • Bensen WG, Laskin CA, Paton TW, Little HA, Fam AG. Twice-daily dosing of enteric-coated aspirin in patients with rheumatic diseases. J Rheumatol. 1979 May–Jun;6(3):351–359. [PubMed]
  • Blechman WJ, Lechner BL. Clinical comparative evaluation of choline magnesium trisalicylate and acetylsalicylic acid in rheumatoid arthritis. Rheumatol Rehabil. 1979 May;18(2):119–124. [PubMed]
  • CASS LJ, FREDERIK WS. A clinical evaluation of chlormeznone and aspirin as an analgesic. N Y State J Med. 1961 Nov 15;61:3856–3861. [PubMed]
  • Cass LJ, Frederik WS. A clinical evaluation of a sustained-release aspirin. Curr Ther Res Clin Exp. 1965 Nov;7(11):683–692. [PubMed]
  • Cass LJ, Frederik WS. Clinical comparison of a sustained- and a regular-release aspirin. Curr Ther Res Clin Exp. 1965 Nov;7(11):673–682. [PubMed]
  • Cassell S, Furst D, Dromgoole S, Paulus H. Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Comparison of two dosage schedules of choline magnesium trisalicylate. Arthritis Rheum. 1979 Apr;22(4):384–388. [PubMed]
  • Furst DE, Tozer TN, Melmon KL. Salicylate clearance, the resultant of protein binding and metabolism. Clin Pharmacol Ther. 1979 Sep;26(3):380–389. [PubMed]
  • Gruber CM, Jr, Bauer RO, Bettigole JB, Lash AF, McDonald JS. A multicenter study for analgesia involving fenoprofen, propoxyphene [alone or in combination] with placebo and aspirin controls in postpartum pain. J Med. 1979;10(1-2):65–98. [PubMed]
  • Harris PA, Riegelman S. Influence of the route of administration on the area under the plasma concentration-time curve. J Pharm Sci. 1969 Jan;58(1):71–75. [PubMed]
  • Hollister LE. Measuring measurin: problems of oral prolonged-action medications. Clin Pharmacol Ther. 1972 Jan–Feb;13(1):1–5. [PubMed]
  • Koch PA, Schultz CA, Wills RJ, Hallquist SL, Welling PG. Influence of food and fluid ingestion on aspirin bioavailability. J Pharm Sci. 1978 Nov;67(11):1533–1535. [PubMed]
  • LASAGNA L. Analgesic drugs. Am J Med Sci. 1961 Nov;242:620–627. [PubMed]
  • Levy G. Aspirin, absorption rate and analgesic effect. Anesth Analg. 1965 Nov–Dec;44(6):837–841. [PubMed]
  • Levy G. Kinetics of pharmacologic effects. Clin Pharmacol Ther. 1966 May–Jun;7(3):362–372. [PubMed]
  • Levy G. Clinical pharmacokinetics of aspirin. Pediatrics. 1978 Nov;62(5 Pt 2 Suppl):867–872. [PubMed]
  • Levy G. Pharmacokinetics of salicylate in man. Drug Metab Rev. 1979;9(1):3–19. [PubMed]
  • Levy G, Giacomini KM. Rational aspirin dosage regimens. Clin Pharmacol Ther. 1978 Mar;23(3):247–252. [PubMed]
  • Levy G, Tsuchiya T. Salicylate accumulation kinetics in man. N Engl J Med. 1972 Aug 31;287(9):430–432. [PubMed]
  • Levy G, Tsuchiya T, Amsel LP. 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. [PubMed]
  • Mäkela AL, Yrjänä T, Mattila M. Dosage of salicylates for children with juvenile rheumatoid arthritis. A prospective clinical trial with three different preparations of acetylsalicylic acid. Acta Paediatr Scand. 1979 May;68(3):423–430. [PubMed]
  • Miller RR. Deafness due to plain and long-acting aspirin tablets. J Clin Pharmacol. 1978 Oct;18(10):468–471. [PubMed]
  • MURRAY WJ. EVALUATION OF ASPIRIN IN TREATMENT OF HEADACHE. Clin Pharmacol Ther. 1964 Jan–Feb;5:21–25. [PubMed]
  • Pachman LM, Olufs R, Procknal JA, Levy G. Pharmacokinetic monitoring of salicylate therapy in children with juvenile rheumatoid arthritis. Arthritis Rheum. 1979 Aug;22(8):826–831. [PubMed]
  • Parkhouse J, Rees-Lewis M, Skolinik M, Peters H. The clinical dose response to aspirin. Br J Anaesth. 1968 Jun;40(6):433–441. [PubMed]
  • Pearson HA. Comparative effects of aspirin and acetaminophen on hemostasis. Pediatrics. 1978 Nov;62(5 Pt 2 Suppl):926–929. [PubMed]
  • REYNOLDS RC, CLUFF LE. Interaction of serum and sodium salicylate: changes during acute infection and its influence on pharmacological activity. Bull Johns Hopkins Hosp. 1960 Nov;107:278–290. [PubMed]
  • Rowland M, Riegelman S, Harris PA, Sholkoff SD. Absorption kinetics of aspirin in man following oral administration of an aqueous solution. J Pharm Sci. 1972 Mar;61(3):379–385. [PubMed]
  • SEED JC. A CLINICAL COMPARISON OF THE ANTIPYRETIC POTENCY OF ASPIRIN AND SODIUM SALICYLATE. Clin Pharmacol Ther. 1965 May–Jun;6:354–358. [PubMed]
  • Seki T. Evaluation of effect of acetylsalicylic acid using electrical stimulation on the forefinger of healthy volunteers. Br J Clin Pharmacol. 1978 Dec;6(6):521–524. [PubMed]
Articles from British Journal of Clinical Pharmacology are provided here courtesy of
British Pharmacological Society

PubMed articles by these authors