Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers.
OBJECTIVE
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 acid-induced 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 TXB(2) 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.
Cox
Dermot
D
Department of Clinical Pharmacology, Royal College of Surgeons, 123 St Stephens Green, Dublin 2, Ireland. dcox@rcsi.ie
Maree
Andrew O
AO
Dooley
Michelle
M
Conroy
Ronán
R
Byrne
Michael F
MF
Fitzgerald
Desmond J
DJ
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D000068342:Aspirin, Dipyridamole Drug Combination; D001835:Body Weight; D018592:Cross-Over Studies; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D012016:Reference Values; D013608:Tablets, Enteric-Coated; D013810:Therapeutic Equivalency; D013929:Thromboxane B2 / Q000097:blood; D016896:Treatment Outcome
D000068342:Aspirin, Dipyridamole Drug Combination; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D013608:Tablets, Enteric-Coated; D013929:Thromboxane B2; D004176:Dipyridamole; D001241:Aspirin