Aspirin Kinetics and Inhibition of Platelet Thromboxane Generation-Relevance for a Solution of the “Aspirin Dilemma”

Abstract

SummarySix healthy male volunteers received aspirin (ASA) in a compressed (320 mg) and an enteric-coated (800 mg) formulation as single oral doses ten days apart. Ten plasma samples were obtained from each volunteer between 5 and 120 min after compressed ASA, and seven between 10 and 240 min after enteric-coated ASA.ASA was undetectable (less than 100 ng/ml) in plasma from three subjects receiving compressed ASA and two receiving the enteric-coated preparation. Plasma levels and kinetic parameters of salicylate were the same in subjects with undetectable and detectable ASA plasma levels.More than 98% inhibition of pre-drug serum TXB2 was noted in all samples collected one and four hours after either ASA preparation. TXB2 generation recovered on average by 3.5% at 24 hr with both preparations.Thus inhibition of platelet TXB2 generation occurred independently of the amount of ASA reaching the peripheral circulation.If this is due to inhibition of platelet function in the enterohepatic circulation followed by extensive first-pass deacetylation of ASA, vascular PGI2 synthesis could be spared.A better knowledge of the kinetic parameters of ASA for each of the formulations used in thrombosis prevention trials might help in solving the “aspirin dilemma”.