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(Stroke. 2006;37:2153.)
© 2006 American Heart Association, Inc.
Original Contributions |
From the Department of Clinical Pharmacology (D.C., A.O.M., M.D., M.F.B., D.J.F.), Royal College of Surgeons, Dublin, Ireland; the School of Pharmacy (D.C.), Royal College of Surgeons, Dublin, Ireland; and the Department of Epidemiology (R.C.), Royal College of Surgeons, Dublin, Ireland.
Correspondence to Dermot Cox, Department of Clinical Pharmacology, Royal College of Surgeons, 123 St Stephens Green, Dublin 2, Ireland. E-mail dcox{at}rcsi.ie
Background and Purpose Aspirin resistance may be relatively common and associated with adverse outcome. Meta-analysis has clearly shown that 75 mg plain aspirin is the lowest effective dose; however, it is not known whether the recent increased use of enteric-coated aspirin could account for aspirin resistance. This study was designed to determine whether enteric-coated aspirin is as effective as plain aspirin in healthy volunteers.
Methods Seventy-one healthy volunteers were enrolled in 3 separate bioequivalence studies. Using a crossover design, each volunteer took 2 different aspirin preparations. Five aspirin preparations were evaluated, 3 different enteric-coated 75-mg aspirins, dispersible aspirin 75 mg and asasantin (25-mg standard release aspirin plus 200-mg modified-release dipyridamole given twice daily). Serum thromboxane (TX) B2 levels and arachidonic acidinduced platelet aggregation were measured before and after 14 days of treatment.
Results All other aspirin preparations tested were inferior to dispersible aspirin (P<0.001) in their effect on serum TXB2 level. Treatment failure (<95% inhibition serum TXB2 formation) occurred in 14 subjects, none of whom were taking dispersible aspirin. Mean weight for those demonstrating treatment failure was greater than those with complete TXB2 (>99%) inhibition (P<0.001). Using logistic regression analysis an 80-kg subject had a 20% probability of treatment failure. Asasantin was the most potent preparation in terms of inhibition of platelet aggregation.
Conclusions Equivalent doses of the enteric-coated aspirin were not as effective as plain aspirin. Lower bioavailability of these preparations and poor absorption from the higher pH environment of the small intestine may result in inadequate platelet inhibition, particularly in heavier subjects.
Key Words: antiplatelet drugs aspirin cyclooxygenase platelet inhibitors
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