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- acetyloxybenzoate, CAS 147249-33-0), a new antiplatelet agent, behaves as a prodrug of acetylsalicylic acid (ASA), metabolism studies in rats were carried out in vivo and in vitro using the whole animal and tissue homogenates. The ASA molecule was not detected in the plasma samples taken after oral administration of aspalatone at 80 mg/kg. Instead, salicylic acid maltol ester (SM), the deacetylated metabolite of aspalatone, was detected in the plasma and it was rapidly hydrolyzed to salicylic acid. In in vitro experiments with rat serum, intestinal fluid, liver and gastric mucosal homogenates, SM was the only compound formed after 4 min incubation at 37 degrees C. From these results it was concluded that aspalatone does not behave as a prodrug of ASA in rats. In addition, the results of experiments using certain esterase inhibitors, suggested the major contribution of B-esterase(s) in the metabolism of aspalatone to SM particularly in serum and intestinal fluid.
Suh
D Y
DY
Natural Products Research Institute, Seoul National University, Korea.
Yang
H O
HO
Kim
Y C
YC
Han
B H
BH
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003640:Dealkylation; D004950:Esterases / Q000037:antagonists & inhibitors; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D011355:Prodrugs; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; D012459:Salicylates; C098446:salicylic acid maltol ester; C091320:aspalatone; D004950:Esterases; D001241:Aspirin