@article {Shimizu1904, author = {Shinji Shimizu and Ryo Atsumi and Tsunenori Nakazawa and Yuko Fujimaki and Kenichi Sudo and Osamu Okazaki}, title = {Metabolism of Ticlopidine in Rats: Identification of the Main Biliary Metabolite as a Glutathione Conjugate of Ticlopidine S-Oxide}, volume = {37}, number = {9}, pages = {1904--1915}, year = {2009}, doi = {10.1124/dmd.109.027524}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {We have identified several novel metabolites of ticlopidine, a well known antiplatelet agent and have revealed its metabolic route in rats. The main biliary metabolite of ticlopidine was characterized as a glutathione (GSH) conjugate of ticlopidine S-oxide, in which conjugation had occurred at carbon 7a in the thienopyridine moiety. Quantitative analysis revealed that 29\% of the dose was subjected to the formation of reactive intermediates followed by conjugation with GSH after oral administration of ticlopidine (22 mg/kg) to rats. In vitro incubation of ticlopidine with rat liver 9000g supernatant fraction (S9) fractions led to the formation of multiple metabolites, including 2-oxo-ticlopidine, the precursor for the pharmacologically active ticlopidine metabolite, [1-(2-chlorobenzyl)-4-mercaptopiperidin-(3Z)-ylidene] acetic acid. A novel thiophene ring-opened metabolite with a thioketone group and a carboxylic acid moiety has also been detected after incubation of 2-oxo-ticlopidine with rat liver microsomes or upon incubation of ticlopidine with rat liver S9 fractions.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/37/9/1904}, eprint = {https://dmd.aspetjournals.org/content/37/9/1904.full.pdf}, journal = {Drug Metabolism and Disposition} }