Coronary Artery Disease
Aspirin absorption rates and platelet inhibition times with 325-mg buffered aspirin tablets (chewed or swallowed intact) and with buffered aspirin solution

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Abstract

Large clinical trials such as the second International Study of Infarct Survival routinely gave patients with myocardial infarction a chewed aspirin, yet there are no data to show whether chewing of aspirin is better, or worse, than swallowing a whole tablet. We performed a randomized, placebo-controlled study to determine whether chewing aspirin or administering it in solution accelerates its absorption and antiplatelet activity. On separate days, 12 fasting volunteers ingested 325 mg of buffered aspirin, either by chewing a tablet for 30 seconds before swallowing it with 4 ounces of water, swallowing a whole tablet with 4 ounces of water, or drinking 4 ounces of Alka Seltzer. Frequent blood samples were obtained for serum aspirin, salicylate, and thromboxane B2 (TxB2) concentrations. With all formulations of aspirin, serum TxB2 decreased 50% when the plasma aspirin concentration reached approximately 1,000 ng/ml. A 50% and 90% decrease in serum TxB2occurred more quickly after chewing a tablet than after a tablet was swallowed whole. For example, the t 50% for serum TxB2 inhibition was 5.0 ± 0.6 minutes with the chewed tablet versus 12.0 ± 2.3 minutes when the tablet was swallowed (p = 0.01). A 50% decrease in serum TxB2 occurred 7.6 ± 1.2 minutes after Alka Seltzer solution (p = 0.04 vs chewing a tablet; p = 0.13 vs swallowing a whole tablet). Chewing an aspirin tablet is the most effective way of accelerating absorption of aspirin into the blood and shortening the time required for an antiplatelet effect.

Section snippets

Subjects

Twelve healthy volunteers (6 women and 6 men) who had not taken ASA or nonsteroidal anti-inflammatory drugs (NSAIDs) within the previous 2 weeks participated in this 6-week, placebo-controlled, randomized, crossover study after giving their informed written consent. The study was approved by the Human Studies Committee of the Dallas VA Medical Center. ASA (other than on study days) and non-ASA NSAIDs were prohibited over the 6-week experimental period. Volunteers’ ages ranged from 21 to 64

Pharmacokinetics of aspirin

When an ASA tablet was chewed, mean plasma ASA concentrations increased rapidly and peaked at between 5,000 and 6,000 ng/ml at 20 minutes (Figure 1, left). Mean plasma salicylate concentration peaked at nearly 20,000 ng/ml at 1 hour (Figure 1, right). Although ASA was no longer detectable in the plasma 3 hours after dosing, salicylate remained detectable throughout the 12-hour experiment. ASA was detectable in the plasma of 10 subjects within 3 minutes of chewing a tablet and in all 12 by 5

Discussion

Other orally administered antiplatelet agents, such as the thienopyridines ticlopidine (Ticlid) and clopidogrel (Plavix), may require several days to inhibit platelet function.9 In contrast, oral ASA inhibits platelet function within a few minutes (see Figure 2). Peak ASA levels in blood were reached in 15 to 20 minutes, nearly identical to what has previously been reported.10

The current ACC/AHA guidelines for management of patients with acute myocardial infarction, based largely on results

Acknowledgements

We wish to thank Kristi Rushin and Kenneth Shewmake for expert technical assistance, Paul Grayburn, MD, Charles Landau, MD, and L. David Hillis, MD, for expert advice, and Vicky Robertson for preparation of the manuscript.

References (15)

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This work was supported by the Department of Veterans Affairs and the Southland Financial Corporation Distinguished Chair in Geriatrics, Dallas, Texas.

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