METABOLIC-FATE OF THE NEW ANTITHROMBOTIC AGENT ASPALATONE IN RATS - IN-VIVO AND IN-VITRO STUDY

In order to determine whether aspalatone ([3-(2-methyl-4-pyronyl)]-2-a cetyloxybenzoate, CAS 147249-33-0), a new antiplatelet agent, behaves as a prodrug of acetylsalicyclic acid (ASA), metabolism studies in rat s were carried out in vivo and in vitro using the whole animal and tis sue homogenates. The ASA molecule was not detected in the plasma sampl es taken after oral administration of aspalatone at 80 mg/kg. Instead, salicylic acid maltol ester (SM), the deacetylated metabolite of aspa latone, was detected in the plasma and it was rapidly hydrolyzed to sa licylic acid. In in vitro experiments with rat serum, intestinal fluid , liver and gastric mucosal homogenates, SM was the only compound form ed after 4 min incubation at 37 degrees C. From these results it was c oncluded that aspalatone does not behave as a prodrug of ASA in rats. In addition, the results of experiments using certain esterase inhibit ors suggested the major contribution of B-esterase(s) in the metabolis m of aspalatone to SM particularly in serum and intestinal fluid.