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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].


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

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