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Nonvegetarians Vegetarians Patients at low-dose aspirin

Figure 2.4 Serum concentrations of salicylic acid (|mM) in nonvegetarians, vegetarians (Buddhist monks of European origin), and patients taking low-dose aspirin (75 mg daily) (modified after Blacklock et al., [44]).

though this possibility certainly exists, the alternative explanation, namely the abdication of (red) meat, the most important natural source not only of cholesterol but also of arachidonic acid (for thromboxane formation), by vegetarians, appears at least as likely.

Gender The possible influence of gender on the pharmacokinetics of aspirin was studied after single (1000 mg) oral, intramuscular or intravenous administration of the (water soluble) lysine salt of aspirin to healthy volunteers. No differences were detected with respect to half-life and distribution volume. The bioavailability after oral and intramuscular administration of standard aspirin was not different between genders, amounting to 54 and 89% in both groups, respectively [45]. The results for low-dose (100 mg) [19] and high-(antirheumatic) dose [46] aspirin were similar though two other small studies found a reduced metabolic capacity for aspirin in women [47, 48]. Taken together, there might be some reduced plasma aspirin hydrolysis rate in women. However, whether these differences in aspirin pharmacokinetics are clinically relevant is questionable. A separate issue is gender-dependent variations in blood alcohol levels after aspirin intake (see above).

Age Bioavailability and metabolism of aspirin are similar in healthy men at the age of 21-40 as compared to those at the age of 55-75. However, in the elderly, there were reduced serum peak levels and a prolonged half-life as opposed to young individuals. This is probably due to the larger volume of distribution for aspirin in elderly persons [49]. However, these age-dependent differences in aspirin bioavailability and metabolism were not considered to play a major role for its therapeutic use [50].

Summary

Standard plain aspirin is poorly soluble in aqueous media at acidic pH. The galenic formulation, the speed of tablet dispersion, the local pH, and velocity of gastric emptying determine the passage time through the stomach and, therefore, stomach (in)tolerance (Section 3.2.1). Absorption of aspirin occurs predominantly in the upper small intestine and is nearly complete there. The systemic bioavailability of standard plain aspirin is about 50% and is reduced to 25-15% or even less after administration as "controlled-release" formulations.

During and after absorption, aspirin undergoes hydrolytic cleavage by esterases in the intestine, portal vein blood, and liver. This results in an equimolar generation ofsalicylic acid, the primary metabolite. Salicylic acid has a larger volume of distribution, in particular, at acidic pH, and accounts for many of the pharmacological actions of aspirin - except inhibition of platelet function. The percentage of free salicylate is dose dependent and increases from about 1% at analgesic doses (1 g) to 30% and more at toxic doses.

Several galenic formulations have been developed to improve gastric tolerance and to modulate the systemic bioavailability of aspirin. For oral use, these are buffered (i.e., easily soluble or predissolved) formulations or (i.v.) administration of aspirin as water-soluble lysine salt. For long-term use, enteric-coated formulations appear to have some advantages.

The bioavailability of aspirin is independent of gender and age. Food intake can reduce the bio-availability of aspirin if this is associated with adsorption to food constituents or a prolonged exposure against esterases in the intestinal mucosa. Otherwise, there are no relevant pharmaco-kinetic interactions between aspirin and other compounds with respect to drug absorption and distribution.

44 | 2 Pharmacology References

1 Horsch, W. (1979) Die Salizylate. Die Pharmazie, 34, 585-604.

2 Cooke, A.R. and Hunt, J.N. (1970) Absorption of acetylsalicylic acid from unbuffered and buffered gastric contents. The American Journal of Digestive Diseases, 2, 95-102.

3 Mason, W.D. and Winer, N. (1983) Influence of food on aspirin absorption from tablets and buffered solutions. Journal of Pharmaceutical Sciences, 72, 819-821.

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

5 Roine, R., Gentry, R.T. and Hernandez-Munoz, R. et al. (1990) Aspirin increases blood alcohol concentrations in humans after ingestion of alcohol. The Journal ofthe American Medical Association, 264, 2406-2408.

6 Melander, O., Liden, A. and Melander, A. (1995) Pharmacokinetic interactions of alcohol and acetylsalicylic acid. European Journal of Clinical Pharmacology, 48, 151-153.

7 Gentry, R.T., Baraona, E., Amir, I. et al. (1999) Mechanism of the aspirin-induced rise in blood alcohol levels. Life Sciences, 65, 2595-2512.

8 Hurtado, C., Acevedo, C., Domecq, C. et al. (1988) Absorption kinetics of acetylsalicylic acid in gastrecto-mized patients. Medical Science Research, 16,1241-1243.

9 Graham, D.Y. and Smith, J.L. (1986) Aspirin and the stomach. Annals of Internal Medicine, 104, 390-398.

10 Cryer, B. and Feldman, M. (1999) Effects of very low dose daily, long-term aspirin therapy on gastric duodenal and rectal prostaglandin levels and on mucosal injury in healthy humans. Gastroenterology, 117, 17-25.

11 Feldmann, R.J. and Maibach, H.I. (1970) Absorption of some organic compounds through the skin of man. Journal of Investigative Dermatology, 54, 399-404.

12 Keimowitz, R.M., Pulvermacher, G., Mayo, G. et al. (1993) Transdermal modification of platelet function. A dermal aspirin preparation selectively inhibits platelet cyclooxygenase and preserves prostacyclin biosynthesis. Circulation, 88, 556-561.

13 McAdam, B., Leimowitz, R.M., Maher, M. et al. (1996) Transdermal modification of platelet function: an aspirin patch system results in marked suppression of platelet cyclooxygenase. The Journal of Pharmacology and Experimental Therapeutics, 277, 559-564.

14 Rowland, M., Riegelman, S., Harris, P.A. et al. (1967) Kinetics of acetylsalicylic acid disposition in man. Nature, 215, 413-414.

15 Rowland, M., Riegelman, S., Harris, P.A. et al. (1972) Absorption kinetics ofaspirin in man following oral administration of an aqueous solution. Journal of Pharmaceutical Sciences, 61, 379-385.

16 Harris, P.A. and Riegelman, S. (1969) Influence ofthe route of administration on the area under the plasma concentration-time curve. Journal ofPharmaceutical Sciences, 58, 71-75.

17 Pedersen, A.K. and FitzGerald, G.A. (1984) Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase. The New England Journal of Medicine, 311, 1206-1211.

18 Siebert, D.J., Bochner, F., Imhoff, D.M. et al. (1983) Aspirin kinetics and platelet aggregation in man. Clinical Pharmacology and Therapeutics, 33, 367-374.

19 Bochner, F., Somogyi, A.A. and Wilson, K.M. (1991) Bioinequivalence of four 100 mg oral aspirin formulations in healthy volunteers. Clinical Pharmacokinetics, 21, 394-399.

20 Cummings, A.J. and Martin, B.K. (1962) Relationship ofplasma salicylate concentration to urinary salicylate excretion rate. Nature, 195, 1104-1105.

21 Cummings, A.J. and King, M.L. (1966) Urinary excretion of acetylsalicylic acid in man. Nature, 209, 620-621.

22 Charman, W.N., Charman, S.A., Monkhouse, D.C. etal. (1993) Biopharmaceutical characterisation of a low-dose (75 mg) controlled-release aspirin formulation. British Journal of Clinical Pharmacology, 36, 470-473.

23 Clarke, R., Mayo, G., Price, P. et al. (1991) Suppression of thromboxane A2 but not of systemic prostacyclin by controlled-release aspirin. The New England Journal of Medicine, 325, 1137-1141.

24 Ligumsky, M., Golanska, E.M., Hansen, D.G. et al. (1983) Aspirin can inhibit gastric mucosal cyclooxygenase without causing lesions in the rat. Gastroenterology, 84, 756-761.

25 Stubbe, L.T., Pietersen, J.H. and Van Heulen, C. (1962) Aspirin preparations and their noxious effect on the gastro-intestinal tract. British Medical Journal, 5279, 675-680.

26 Mason, W.D. (1984) Comparative aspirin absorption kinetics after administration of sodium- and potassium-containing buffered solutions. Journal of Pharmaceutical Sciences, 73, 998-999.

27 Dromgoole, S.H. and Furst, D.E. (1992) Salicylates, in Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring (eds W.E. Evans, J.J. Schentag and W.J. Jusko), Lippincott Williams & Wilkins.

28 Cohen, L.S. (1976) Clinical pharmacology of acetylsalicylic acid. Seminars in Thrombosis and Hemostasis, 2, 146-175.

29 Green, F.A. and Young, C.Y. (1981) Acetylation of erythrocytotic membrane peptides by aspirin. Transfusion, 21, 55-58.

30 Gaspari, F., Vigano, G., Orisio, S. et al. (1987) Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition. The Journal of Clinical Investigation, 79, 1788-1797.

31 Ghahramani, P., Rowland-Yeo, K., Yeo, W.W. et al. (1998) Protein binding of aspirin and salicylate measured by in vivo ultrafiltration. Clinical Pharmacology and Therapeutics, 68, 285-295.

32 Bromm, B., Rundshagen, I. and Scharein, E. (1991) Central analgesic effects of acetylsalicylic acid in healthy men. Arzneimittel-Forschung/Drug Research, 41, 1123-1129.

33 Smith, M.J.H. and Dawkins, P.D. (1971) Salicylate and enzymes. The Journal of Pharmacy and Pharmacology, 23, 729-744.

34 Insel, P.A. (1990) Analgesic, antipyretic and antiinflammatory agents: drugs employed in the treatment of rheumatoid arthritis and gout, in Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th edn, Pergamon Press, New York, pp. 638-681.

35 Sholkoff,S.D., Eyring, J.E., Rowland, M. et al. (1967) Plasma and synovial fluid concentrations of acetylsalicylic acid in patients with rheumatoid arthritis. Arthritis and Rheumatism, 10, 348-351.

36 Bannwarth, B., Netter, P., Pourel, J. et al. (1989) Clinical pharmacokinetics of nonsteroidal anti-inflammatory drugs in the cerebrospinal fluid. Biomedicine & Pharmacotherapy, 43, 121-126.

37 Palmisano, P.A. and Cassady, G. (1969) Salicylate exposure in the perinate. The Journal ofthe American Medical Association, 209, 556-558.

38 Winstanley, P.A. and Orme, M.L. (1989) The effects of food on drug bioavailability. British Journal ofClinical Pharmacology, 28, 621-628.

39 Koch, P.A., Schultz, C.A., Wills, R.J. et al. (1978) Influence of food and fluid ingestion on aspirin bioavailability. Journal of Pharmaceutical Sciences, 67, 1533-1535.

40 Ferner, R.E., Williams, F.M., Graham, M. et al. (1989) The metabolic effects of aspirin in fasting and fed subjects. British Journal of Clinical Pharmacology, 27,104.

41 Mojaverian, P., Rocci, M.L., Jr, Conner, D.P. etal. (1987) Effect of food on the absorption of enteric-coated aspirin: correlationwithgastricresidencetime. Clinical Pharmacology and Therapeutics, 41, 11-17.

42 Janssen, P.L.T.M.,Katan, M.B.,vanStaveren,W.A.etal. (1997) Acetylsalicylate and salicylates in foods. Cancer Letters, 114, 163-164.

43 Baxter, G.J., Lawrence, J.R., Graham, A.B. et al. (2002) Identification and determination of salicylic acid and salicyluric acid in urine of people not taking salicylate drugs. Annals of Clinical Biochemistry, 39, 50-55.

44 Blacklock, C.J., Lawrence, J.R., Wiles, D. et al. (2001) Salicylic acid in the serum of subjects not taking aspirin. Comparison of salicylic acid concentrations in the serum of vegetarians, non-vegetarians, and patients taking low-dose aspirin. Journal of Clinical Pathology, 54, 553-555.

45 Aarons, L.K., Hopkins, M., Rowland, S. et al. (1989) Route of administration and sex differences in the pharmacokinetics of aspirin administered as its lysine salt. Pharmacological Research, 6, 660-666.

46 Rainsford, K.D., Ford, N.L.V., Brooks, P.M. etal. (1980) Plasma aspirin esterases in normal individuals, patients with alcoholic liver disease and rheumatoid arthritis: characterization and the importance of the enzymic components. European Journal of Clinical Investigation, 10, 413-420.

47 Ho, P.C., Triggs, E.J., Bourne, D.W. et al. (1985) The effects of age and sex on the disposition ofacetylsalicylic acid and its metabolites. British Journal of Clinical Pharmacology, 19, 675-684.

48 Miners, J.O., Grgurinovich, N., Whitehead, A.G. et al. (1986) Influence of gender and oral contraceptive steroids on the metabolism of salicylic acid and acetylsalicylic acid. British Journal of Clinical Pharmacology, 22, 135-142.

49 Mason, W.D., Falbe, J.W., Fu, C.H.J. et al. (1989) Comparative aspirin bioavailability in young and old men. Pharmaceutical Research, 6 (Suppl. 9), S233.

50 Montgomery, P.R., Berger, L.G., Mitenko, P.A. et al. (1986) Salicylate metabolism: effect of age and sex in adults. Clinical Pharmacology and Therapeutics, 39, 571-576.

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