Skip to main content

Monitoring Plasma Concentrations of Salicylate

Abstract

Measurement of the plasma concentration of salicylate has been made in the majority of clinical settings where salicylates, mostly in the form of acetylsalicylic acid (aspirin), are used extensively to treat chronic rheumatic conditions. At the same time, studies on the kinetics of salicylates have increased in the specialised literature. Analysis of published papers suggests a surprising difference between principles documented in controlled situations and what happens in routine clinical practice. Recommended dosage regimens are based on a rather narrow amount of data, as relevant studies include few patients and have not used readily comparable protocols.

The wealth of information available on the kinetics and metabolism of salicylates has not yet produced generally accepted agreement on how to achieve optimum therapeutic results. Plasma concentration monitoring programmes aim mainly at avoiding side effects and checking compliance, but do not deal specifically with overall evaluation of therapeutic outcome. In the longer term, aspirin may possibly become less favoured as the initial drug of choice for the treatment of chronic rheumatic conditions, and the merits of monitoring plasma salicylate levels could be even less favoured. In the meantime, however, as clinical practice still largely involves use of aspirin, prospective collection of more controlled data on larger population groups seems warranted, not only for the benefit of treated patients but also for the purpose of assessing more thoroughly the clinical relevance of therapeutic drug monitoring in this area.

This is a preview of subscription content, access via your institution.

References

  • Abrishami, M.A. and Thomas, J.: Aspirin intolerance — A review. Annals of Allergy 39: 28–37 (1977).

    PubMed  CAS  Google Scholar 

  • Ali, M.A. and Routh, J.I.: The protein binding of acetylsalicylic acid and salicylic acid, Clinical Chemistry 15: 1027–1038 (1969).

    PubMed  CAS  Google Scholar 

  • Ali Laik, S.: A comparative study of the derivatization of salicylic acid and acetylsalicylic acid with BSTFA, MSTFA and methyl rodide in presence of potassium carbonate prior to GLC determination. Chromatografia 8: 33–34 (1975).

    Article  Google Scholar 

  • Ali, M.; McDonald, J.W.; Thiessen, J.J. and Coates, P.E.: Plasma acelylsalicylate and salicylate and platelet cyclooxygenase activity following plain and enteric-coated aspirin, Stroke 11: 9–13 (1980).

    PubMed  CAS  Article  Google Scholar 

  • American Pharmaceutical Association: Evaluations of Drug Interactions, 2nd. ed, (APA, Washington, 1976).

  • Ascione, P.P. and Chrekian, G.P.: Automated high-pressure liquid chromatographic analysis of aspirin, phenacetin, and caffeine. Journal of Pharmaceutical Sciences 64: 1029–1033 (1979).

    Article  Google Scholar 

  • Athreya, B.H.; Moser, G.; Cecil, H.S. and Myers, A.R.: Aspirin-induced hepatotoxicity in juvenile rheumatoid arthritis, A prospective study. Arthritis and Rheumatism 18: 347–352 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Bardare, M.; Chislaghi, G.U.; Mandelli, M. and Sereni, F.: Value of monitoring plasma salicylate levels in treating juvenile rheumatoid arthritis: observations in 42 cases. Archives of Disease in Childhood 53: 381–385 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Bedford, C.; Cummings, A.J. and Martin, B.K.: A kinetic study of the elimination of salicylate in man. British Journal of Pharmacology 24: 418–431 (1965).

    CAS  Google Scholar 

  • Bender, K.J.: Salicylate intoxication. Drug Intelligence and Clinical Pharmacy 9: 350–360 (1975).

    CAS  Google Scholar 

  • Berg, K.J.: Acute acetylsalicylic acid poisoning: Treatment with forced alkaline diuresis and diuretics. European Journal of Clinical Pharmacology 12: 111–116 (1977a).

    PubMed  CAS  Article  Google Scholar 

  • Berg, K.J.: Acute effects of acetylsalicylic acid in patients with chronic renal insufficiency. European Journal of Clinical Pharmacology 11: 111–116 (1977b).

    PubMed  CAS  Article  Google Scholar 

  • Berg, K.J.: Acute effects of acetylsalicylic acid on renal function in normal man. European Journal of Clinical Pharmacology 11: 117–123 (1977c).

    PubMed  CAS  Article  Google Scholar 

  • Bernstein, B.H.; Singsen, B.H.; King, K.K. and Hanson, V.: Aspirin-induced hepatotoxicity and its effect on juvenile rheumatoid arthritis. American Journal of Diseases of Children 131: 659–663 (1977).

    PubMed  CAS  Google Scholar 

  • Bernstein, S.H. and Allerhand, J.: Abnormalities or serum proteins as criteria for the diagnosis of acute rheumatic fever. American Journal of Medical Sciences 247: 431–437 (1964).

    CAS  Article  Google Scholar 

  • Blair, D.; Rumack, B.H. and Peterson, R.G.: Analysis for salicylic acid in serum by high-performance liquid chromatography. Clinical Chemistry 24: 1543–1544 (1978).

    PubMed  CAS  Google Scholar 

  • Borga, O.; Odar-Cederlöf, I.; Ringberger, V.-A. and Norlin, A.: Protein binding of salicylate in uremic and normal plasma. Clinical Pharmacology and Therapeutics 20: 464–475 (1976).

    PubMed  CAS  Google Scholar 

  • Brown, S.S.; Cameron, J.C. and Matthew, H.: Plasma salicylate levels in acute poisoning in adults. British Medical Journal 2: 738–739 (1967).

    PubMed  CAS  Article  Google Scholar 

  • Buchanan, N. and Rabinowitz, L.: Infantile salicylism — A reappraisal. Journal of Pediatrics 84: 391–395 (1974).

    PubMed  CAS  Article  Google Scholar 

  • Calabro, J.J.; Burnstein, S.L. and Staley, H.L.: Letter to the Editor. Scandinavian Journal of Rheumatology 5: 251–252 (1976).

    PubMed  CAS  Article  Google Scholar 

  • Cassell, S.; Furst, D.; Dromgoole, S. and Paulus, H.: Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Arthritis and Rheumatism 22: 384–388 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Chiou, W. and Onyemelukwe, I.: Disintegration, dissolution and oral absorption in humans of five commercial buffered aspirin dosage form. Journal of Clinical Pharmacology 14: 597–603 (1974).

    PubMed  CAS  Google Scholar 

  • Coldwell, B.B.; Solomonraj, G.; Boyd, E.M.; Jante, J. and Morrison, A.B.: The effect of dosage from and route of administration on the absorption and excretion of acetylsalicylic acid in man. Clinical Toxicology 2: 111–127 (1969).

    Article  Google Scholar 

  • Craig, J.O.; Ferguson, I.C. and Syme, J.: Infants, toddlers and aspirin. British Medical Journal 1: 757–761 (1966).

    PubMed  CAS  Article  Google Scholar 

  • Cummings, A.J.; Martin, B.K. and Renton, R.: The elimination of salicylic acid in man: serum concentrations and urinary excretion rates. British Journal of Pharmacology 26: 461–467 (1966).

    CAS  Google Scholar 

  • Davies, M.G.; Vella Briffa, D. and Greaves, M.W.: Systemic toxicity from topically applied salicylic acid. British Medical Journal 1: 661 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Davison, C.: Salicylate metabolism in man. Annals of the New York Academy of Sciences 179: 249–268 (1971).

    PubMed  CAS  Article  Google Scholar 

  • Davison, C. and Mandel, H.G.: Nonnarcotic analgesics and antipyretics, 1. Salicylates; in Di Palma (Ed.) Drill’s Pharmacology in Medicine, pp. 379–403 (McGraw-Hill, New York 1971).

    Google Scholar 

  • Davison, C. and Smith, P.K.: The binding of salicylic acid and related substances to purified proteins. Journal of Pharmacology and Experimental Therapeutics 133: 161–170 (1961).

    PubMed  CAS  Google Scholar 

  • Day, R.; Shen, D. and Azarnoff, D.: Decline of steady-state serum salicylate in rheumatoid arthritis given high-dosage salicylate therapy. Clinical Pharmacology and Therapeutics 25: 220–221 (1979).

    Google Scholar 

  • Dick, W.C.; Gibson, R.; Gray, G.I.L. and Buchanan, W.W.: Salicylates and homeopathy. British Journal of Clinical Pharmacology 7: 530–531 (1979).

    Google Scholar 

  • Done, A.K.: Significance of measurements of salicylate in blood in case of acute ingestion. Pediatrics 26: 800–807 (1960).

    PubMed  CAS  Google Scholar 

  • Done, A.K.: Salicylate, pharmacokinetics, and the Pediatrician. Pediatrics 54: 670–672 (1974).

    PubMed  CAS  Google Scholar 

  • Doughty, R.A.; Gresecke, L. and Athreya, B.: Prospective study of salicylate therapy in juvenile rheumatoid arthritis. Dosage-serum salicylate levels and clinical/biochemical toxicity. Clinical Pharmacology and Therapeutics 25: 221 (1979).

    Google Scholar 

  • Edwards, L.J.: Dissolution and diffusion of aspirin in aqueous media. Trans Faraday Society 47: 1191–1210 (1951).

    CAS  Article  Google Scholar 

  • Ekstrand, R.; Alvan, G. and Borgå, O.: Concentration dependent plasma protein binding of salicylate in rheumatoid patients. Clinical Pharmacokinetics 4: 137–143 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Elliott, H.C.: Urinary excretion kinetics of salicyluric acid. Proceedings of the Society for Experimental Biology and Medicine 121: 861–864 (1966).

    PubMed  CAS  Google Scholar 

  • Furst, D.E.; Gupta, N. and Paulus, H.E.: Evidence suggesting a genetic influence and induction of salicylurate formation. Journal of Clinical Investigation 60: 32–42 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Gibaldi, M.; Grundhofer, B. and Levy, G.: Time course and dose dependence of antacid effect on urine pH. Journal of Pharmaceutical Sciences 64: 2003–2004 (1975).

    PubMed  CAS  Article  Google Scholar 

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

    PubMed  CAS  Article  Google Scholar 

  • Gibson, R.G.; Gibson, S.L.M.; MacNeill, A.D.; Gray, G.H.; Dick, W.C. and Buchanan, W.W.: Salicylates and homeopathy in rheumatoid arthritis: preliminary observations. British Journal of Clinical Pharmacology 6: 391–395 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Graham, G.G.; Champion, G.D.; Day, R.O. and Pauli, P.D.: Patterns of plasma concentrations and urinary excretion of salicylate in rheumatoid arthritis. Clinical Pharmacology and Therapeutics 22: 410–420 (1977).

    PubMed  CAS  Google Scholar 

  • Gunsberg, M.; Cham, B.E.; Imhoff, D.M.; Parsons, G.; Bochner, F. and Johnson, F.L.: Correlation of aspirin dose with concentrations of salicylic acid in plasma, plasma water and saliva and clinical response in patients with rheumatoid disease. Australian and New Zealand Journal of Medicine 10: 268–278 (1980).

    Article  Google Scholar 

  • Gupta, N.; Sarkissian, E. and Paulus, H.E.: Correlation of plateau serum salicylate level with rate of salicylate metabolism. Clinical Pharmacology and Therapeutics 18: 350–355 (1975).

    PubMed  CAS  Google Scholar 

  • Harris, P.A. and Riegelman, S.: Acetylsalicylic acid hydrolysis in human blood and plasma. I. Methodology and in vitro studies. Journal of Pharmaceutical Sciences 56: 713–716 (1967).

    PubMed  CAS  Article  Google Scholar 

  • Hill, J.B.: The effect of altering blood pH on rat tissue and plasma salicylate concentrations. Federation Proceedings 29: 434 proc. (1970).

    Google Scholar 

  • Hill, J.B.: Salicylate intoxication. New England Journal of Medicine 288: 1110–1113 (1973).

    PubMed  CAS  Article  Google Scholar 

  • Hill, J.B. and Smith, R.M.: An automated microfluoromatic determination after salicylate in body fluids and tissue extracts. Biochemical Medicine 4: 24–35 (1970).

    PubMed  CAS  Article  Google Scholar 

  • Hollister, L. and Levy, G.: Some aspects of salicylate distribution and metabolism in man. Journal of Pharmaceutical Sciences 54: 1126–1129 (1965).

    PubMed  CAS  Article  Google Scholar 

  • Huston, G.: Salicylates and homeopathy. British Journal of Clinical Pharmacology 7: 529–530 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Jick, H. and Porter, J.: Drug-induced gastrointestinal bleeding. Lancet 2: 87–89 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Klinenberg, J.R. and Miller, F.: Effect of corticosteroids on blood salicylate concentration. Journal of the American Medical Association 194: 601–604 (1965).

    PubMed  CAS  Article  Google Scholar 

  • Kramer, E, and Routh, J.I.: The binding of salicylic acid and acetylsalicylic acid to human serum albumin. Clinical Biochemistry 6: 98–105 (1973).

    PubMed  CAS  Article  Google Scholar 

  • Kucera, J.L. and Bullock, F.J.: The binding of salicylate to plasma protein from several animal species. Journal of Pharmacy and Pharmacology 21: 293–296 (1969).

    PubMed  CAS  Article  Google Scholar 

  • Lainhaw, D.A.: Rheumatoid arthritis improved by treatment with levamisole and L-histoline. Medical Journal of Australia 2: 382–385 (1976).

    Google Scholar 

  • Leonards, J.R.: The influence of solubility on the rate of gastrointestinal absorption of aspirin. Clinical Pharmacology and Therapeutics 4: 476–479 (1963).

    PubMed  CAS  Google Scholar 

  • Leonards, J.R. and Levy, C.: Absorption and metabolism of aspirin administered in enteric coated tablets. Journal of American Medical Association 193: 99–104 (1965).

    CAS  Article  Google Scholar 

  • Levy, G.: Salicylurate formation — demonstration of Michaelis-Menten kinetics in man. Journal of Pharmaceutical Sciences 54: 496 (1965a).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G.: Comparison of dissolution and absorption rates of different commercial aspirin tablets. Journal of Pharmaceutical Sciences 50: 388–392 (1961).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G.: Effect of certain tablet formulation factors on dissolution rate of the active ingredient. I. Journal of Pharmaceutical Sciences 52: 1039–1046 (1963).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G.: Pharmacokinetics of salicylate elimination in man. Journal of Pharmaceutical Sciences 54: 959–967 (1965b).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G. and Garrettson, L.K.: Kinetics of salicylate elimination by newborn infants of mothers who ingested aspirin before delivery. Pediatrics 53: 201–210 (1974).

    PubMed  CAS  Google Scholar 

  • Levy, G. and Giacomini, K.M.: Rational aspirin dosage regimens. Clinical Pharmacology and Therapeutics 23, 247–252 (1978).

    PubMed  CAS  Google Scholar 

  • Levy, G. and Gumlow, R.H.: Effect of certain tablet formulation factors on dissolution rate of active ingredients. III. Tablet lubricants. Journal of Pharmaceutical Sciences 52: 1139–1144 (1963).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G. and Hollister, L.E.: Inter- and intrasubject variations in drug absorption kinetics. Journal of Pharmaceutical Sciences 53: 1446–1452 (1964).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G. and Leonards, J.R.: Absorption, metabolism and excretion of salicylates: in Smith and Smith (Eds.) The Salicylates: A critical bibliographic review. pp.5–48 (Interscience, New York 1966).

    Google Scholar 

  • Levy, G. and Tsuchiya, T.: Salicylate accumulation kinetics in man. New England Journal of Medicine 287: 430–432 (1972).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G. and Tsuchiya, T.: Effect of activated charcoal on aspirin absorption in man. I. Clinical Pharmacology and Therapeutics 13: 317–322 (1972b).

    PubMed  CAS  Google Scholar 

  • Levy, G. and Yaffe, S.J.: The study of salicylate pharmacokinetics in intoxicated infants and children. Clinical Toxicology 1: 409–424 (1968).

    Article  Google Scholar 

  • Levy, G. and Yaffe, S.J.: Relationship between dose and apparent volume of distribution of salicylate in children. Pediatrics 54: 713–717 (1974).

    PubMed  CAS  Google Scholar 

  • Levy, G.; Amsel, L.P. and Elliott, H.C.: Kinetics of salicyluric acid elimination in man. Journal of Pharmaceutical Sciences 58: 827–829 (1969a).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G.; Procknal, J.A. and Garrettson, L.K.: Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium. Clinical Pharmacology and Therapeutics 18: 210–214 (1975a).

    PubMed  CAS  Google Scholar 

  • Levy, O.; Vogel, A.W. and Amsel, L.P.: Capacity-limited salicylurate formation during prolonged administration of aspirin to healthy human subjects. Journal of Pharmaceutical Sciences 58: 503–504 (1969b).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G.; Tsuchiya, T. and Amsel, L.P.: 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.; Lampman, T.; Kamath, B.L. and Garrettson, L.K.: Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid. New England Journal of Medicine 293: 323–325 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G.; Baliah, T. and Procknal, J.A.: Effect of renal transplantation on protein binding of drugs in serum of donor and recipient. Clinical Pharmacology and Therapeutics 20: 512–516 (1976).

    PubMed  CAS  Google Scholar 

  • Lieberman, S.V. and Wood, J.M.: Aspirin formulation and absorption rate. II. Influence on serum levels of tablets, antiacids and solutions. Journal of Pharmaceutical Sciences 53: 1492–1495 (1964).

    PubMed  CAS  Article  Google Scholar 

  • Levy, G.; Procknal, J.A.; Olufs, B.A.R. and Pachman, L.M.: Relationship between serum salicylate concentration and free or total salicylate concentration in serum of children with juvenile rheumatoid arthritis. Clinical Pharmacology and Therapeutics 27: 619–627 (1980).

    PubMed  CAS  Article  Google Scholar 

  • Macpherson, C.R.; Milne, M.D. and Evans, B.M.: The excretion of salicylate. British Journal of Pharmacology 10: 484–489 (1955).

    CAS  Google Scholar 

  • Mäkelä, A.-L.; Yrjänä, T. and Haapasaari, J.: Dosage of salicylates for children with juvenile rheumatoid arthritis. Scandinavian Journal of Rheumatology 4, 250–252 (1975).

    PubMed  Article  Google Scholar 

  • Mäkelä, A.L.; Yrjänä, T. and Mattila, M.: Dosage of salicylate for children with juvenile rheumatoid arthritis. Acta Paediatrica Scandinavica 68: 423–430 (1979).

    PubMed  Article  Google Scholar 

  • Miller, R.L. and Melmon, K.L.: Inflammatory disorders; in Morrelli and Melmon (Eds.) Clinical Pharmacology, pp.382–417 (MacMillan, New York 1972).

    Google Scholar 

  • Miller, R.R.: Deafness due to plain and long acting aspirin tablets. Journal Clinical Pharmacology 18: 468–471 (1978).

    CAS  Google Scholar 

  • Mitchell, I.: ‘Therapeutic’ salicylate poisoning in children. British Medical Journal 1: 1081 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Mongan, E.; Kelly, P.; Nies, K.; Porter, W.W. and Paulus, H.E.: Tinnitus as an indication of therapeutic serum salicylate levels. Journal of American Medical Association 226: 142–145 (1973).

    CAS  Article  Google Scholar 

  • Muller, F.O.; Thundt, H.K.L. and Muller, D.G.: Pharmacokinetic and pharmacodynamic implications of long-term administration of non steroidal antiinflammatory agents. International Journal of Clinical Pharmacology 15: 397 (1977).

    CAS  Google Scholar 

  • Muni, I.A.; Leeling, J.L.; Helms, R.J.; Johnson, N.; Bare, J.J. and Phillips, B.M.: Improved colorimetric determination of aspirin and salicylic acid concentrations in human plasma. Journal of Pharmaceutical Sciences 67: 289–291 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Nikelly, J.G.: Gas chromatographic determination of acetylsalicylic acid in the blood. Analytical Chemistry 36: 2248–2250 (1964).

    CAS  Article  Google Scholar 

  • Nowak, M.M., Brundhofer, B. and Gibaldi, M.: Rectal absorption from aspirin suppositories in children and adults. Pediatrics 54: 23–26 (1974).

    PubMed  CAS  Google Scholar 

  • O’Gorman, T. and Koff, R.S.: Salicylate hepatitis. Gastroenterology 72: 726–8 (1977).

    PubMed  Google Scholar 

  • Pachman et al.: Pharmacokinetic monitoring of salicylate therapy in children with juvenile rheumatoid arthritis. Arthritis and Rheumatism 22: 826–831 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Paulus, H.E. and Whitehouse, M.W.: Nonsteroid anti-inflammatory agents. Annual Review of Pharmacology 13: 107–125 (1973).

    PubMed  CAS  Article  Google Scholar 

  • Paulus, H.E.; Siegel, M.; Mongan, E.; Okun, R. and Calabro, J.J.: Variations of serum concentrations and half life of salicylate in patients with rheumatoid arthritis. Arthritis and Rheumatism 14: 527–532 (1971).

    PubMed  CAS  Article  Google Scholar 

  • Peng, G.W.; Gadalla, M.A.F.; Smith, V.; Peng, A. and Chiou, W.L.: Simple and rapid high-pressure liquid chromatographic simultaneous determination of aspirin, salicylic acid, and salicyluric acid in plasma. Journal of Pharmaceutical Sciences 67: 710–712 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Pierce, A.W. Jr.: Salicylate poisoning. Pediatrics 54: 342–347 (1974).

    PubMed  CAS  Google Scholar 

  • Rance, M.J.; Jordan, B.J. and Nichols, J.D.: A simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in plasma by gas liquid chromatography. Journal of Pharmacy and Pharmacology 27: 425–429 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Reynolds, R.C. and Cluff, L.E.: Interaction of serum and sodium salicylate: changes during acute infection and the influence on pharmacological activity. Bulletin of Johns Hopkins Hospital 107: 278–290 (1960).

    CAS  Google Scholar 

  • Richens, A. and Warrington, S.: When should plasma drug levels be monitored? Drugs 17: 488–500 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Routh, J.I.; Shane, N.A.; Arredondo, F.G. and Paul, W.D.: Method for the determination of acetylsalicylic acid in the blood. Clinical Chemistry 13: 734–743 (1967).

    PubMed  CAS  Google Scholar 

  • Rowland, M. and Riegelman, S.: Pharmacokinetics of acetylsalicylic acid and salicylic acid after intravenous administrations in man. Journal of Pharmaceutical Sciences 57: 1313–1319 (1968).

    CAS  Article  Google Scholar 

  • Rowland, M.; Riegelman, S.; Harris, P.A.; Sholkoff, S.D. and Eyring, E.J.: Kinetics of acetylsalicylic acid disposition in man. Nature 215: 413–414 (1967).

    PubMed  CAS  Article  Google Scholar 

  • Rowland, M.; Riegelman, S.; Harris, P.A. and Sholkoff, S.D.: Absorption kinetics of aspirin in man following oral administration of an aqueous solution. Journal of Pharmaceutical Sciences 61: 379–385 (1972).

    PubMed  CAS  Article  Google Scholar 

  • Rumble, R.H.; Brooks, P.M. and Roberts, M.S.: Interaction between levamisole and aspirin in man. British Journal of Clinical Pharmacy 7: 631–633 (1979).

    CAS  Article  Google Scholar 

  • Rumble, R.H.; Brooks, P.M. and Robertz, M.S.: Metabolism of salicylate during chronic aspirin therapy. British Journal of Clinical Pharmacology 9: 41–45 (1980).

    PubMed  CAS  Article  Google Scholar 

  • Salem, S.A.M. and Stevenson, I.H.: Absorption kinetics of aspirin and quinine in elderly subjects. British Journal of Clinical Pharmacology 4: 397P (1977).

    Article  Google Scholar 

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

    PubMed  CAS  Article  Google Scholar 

  • Sholkoff, S.D.; Eyring, E.J.; Rowland, M. and Riegelman, S.: Plasma and synovial fluid concentrations of acetylsalicylic acid in patients with rheumatoid arthritis. Arthritis and Rheumatism 10: 348–351 (1967).

    PubMed  CAS  Article  Google Scholar 

  • Smith, M.J.M.: Plasma-salicylate concentrations after small doses of acetylsalicylic acid. Journal of Pharmacy and Pharmacology 3: 409–414 (1951).

    PubMed  CAS  Article  Google Scholar 

  • Smith, P.K.; Gleason, H.L.; Stoll, C.G. and Ogorzalek, S.: Studies on the pharmacology of salicylates. Journal of Pharmacology and Experimental Therapeutics 87: 237–255 (1946).

    PubMed  CAS  Google Scholar 

  • Smyth, C.J. and Bravo, J.F.: Antirheumatic drugs: clinical pharmacological and therapeutic aspects. Drugs 10: 394–425 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Soren, A.: Kinetics of salicylates in blood and joint fluids. Journal of Clinical Pharmacology 15: 173–177 (1975).

    PubMed  CAS  Google Scholar 

  • Spector, R.; Korkin, D.T. and Lorenzo, A.V.: A rapid method for the determination of salicylate binding by the use of ultrafilters. Journal of Pharmacy and Pharmacology 24: 786–789 (1972).

    PubMed  CAS  Article  Google Scholar 

  • Stevenson, G.W.: Rapid ultraviolet spectrophotometric determination of salicylate in blood. Analytical Chemistry 32: 1522–1525 (1960).

    CAS  Article  Google Scholar 

  • Stevenson, R.L. and Burtis, C.A.: The analysis of aspirin and related compounds by liquid chromatography. Journal of Chromatography 61: 253–261 (1971).

    PubMed  CAS  Article  Google Scholar 

  • Talberl, R.L.; Ludden, T.M. and West, R.E.: Rapid establishment of therapeutic serum concentrations of salicylates. Journal of Clinical Pharmacology 19: 108–112 (1979).

    Google Scholar 

  • Talbert, R.L.; Ludden, T.M.; Littlefield, L.C. and Reed, W.E.: Development of a loading regimen for aspirin. Current Therapeutic Research 27: 584–594 (1980).

    Google Scholar 

  • Thomas, B.H.; Solomonraj, G. and Coldwell, B.B.: The estimation of acetylsalicylic acid and salicylate in biological fluids by gas-liquid chromatography. Journal of Pharmacy and Pharmacology 25: 201–204 (1973).

    PubMed  CAS  Article  Google Scholar 

  • Tognoni, G.; Bellantuono, C.; Bonati, M.; D’Incalci, M.; Gerna, M.; Latini, R.; Mandelli, M.; Porro, M.G. and Riva, E.: Clinical relevance of pharmacokinetics. Clinical Pharmacokinetics 5: 105–136 (1980).

    PubMed  CAS  Article  Google Scholar 

  • Tognoni, G.; Lakin, R. and Jusko, W.W. (Eds). Frontiers in Therapeutic Drug Monitoring (Raven Press, 1980).

  • Trinder, P.: Rapid determination of salicylate in biological fluids. Biochemical Journal 57: 301–303 (1954).

    PubMed  CAS  Google Scholar 

  • Tsuchiya, T. and Levy, G.: Relationship between dose and plateau levels of drugs eliminated by parallel first-order and capacity-limited kinetics. Journal of Pharmaceutical Sciences 61: 541–544 (1972a).

    PubMed  CAS  Article  Google Scholar 

  • Tsuchiya, T. and Levy, C.: Biotransformation of salicylic acid to its acyl and phenolic glucuronides in man. Journal of Pharmaceutical Sciences 61: 800–801 (1972b).

    PubMed  CAS  Article  Google Scholar 

  • Vesell, E.S.: Relationship between drug distribution and therapeutic effects in man. Annual Review of Pharmacology 14: 249–270 (1974).

    CAS  Article  Google Scholar 

  • Walter, L.J.; Biggs, D.F. and Coutts, R.T.: Simultaneous GLC estimation of salicylic acid and aspirin in plasma. Journal of Pharmaceutical Sciences 63: 1754–1758 (1974).

    PubMed  CAS  Article  Google Scholar 

  • Watson, J.R.; Crescuolo, P. and Fumi Matsui: Rapid simultaneous determination of salicylic acid and aspirin by GC/I: analysis of synthetic aspirin-salicylic acid mixtures and of single-component aspirin tablets. Journal of Pharmaceutical Sciences 60: 454–458 (1971).

    PubMed  CAS  Article  Google Scholar 

  • Wiegand, R.G. and Sanders, P.C.: Calculation of kinetic constants from blood levels of drugs. Journal of Pharmacology and Experimental Therapeutics 146: 271–275 (1964).

    PubMed  CAS  Google Scholar 

  • Williams, L.A.; Linn, R.A. and Zak, B.: Differential ultraviolet spectrophotometric determination of serum salicylates. Journal of Laboratory and Clinical Medicine 53: 156–162 (1959).

    PubMed  CAS  Google Scholar 

  • Wilson, J.T.; Howell, R.L.; Holladay, M.W.; Brilis, G.M.; Chrastil, J.; Watson, J.T. and Taber, D.F.: 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 

  • Wolfe, J.D.; Metzger, A.L. and Goldstein, R.C.: Aspirin hepatitis. Annals of Internal Medicine 80: 74–76 (1974).

    PubMed  CAS  Google Scholar 

  • Wosilait, W.D.: Theoretical analysis of the binding of salicylate by human serum albumin: The relationship between free and bound drug and therapeutic levels. European Journal of Clinical Pharmacology 9: 285–290 (1976).

    PubMed  CAS  Article  Google Scholar 

  • Wurster, D.E. and Kramer, S.F.: Investigation of some factors influencing percutaneous absorption. Journal of Pharmaceutical Sciences 50: 288–293 (1961).

    PubMed  CAS  Article  Google Scholar 

  • Yacobi, A. and Levy, G.: Intraindividual relationship between serum protein binding of drug in normal human subjects, patients with impaired renal function, and rats. Journal of Pharmaceutical Sciences 66: 1285–1288 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Zimmerman, H.J.: Editorial: Aspirin-induced hepatic injury. Annals of Internal Medicine 80: 103–105 (1974).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mandelli, M., Tognoni, G. Monitoring Plasma Concentrations of Salicylate. Clin Pharmacokinet 5, 424–440 (1980). https://doi.org/10.2165/00003088-198005050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198005050-00002

Keywords

  • Aspirin
  • Salicylic Acid
  • Salicylate
  • Rheumatoid arthritIS
  • Salicylic Acid Concentration