The objective of this investigation was to compare the efficiency of conversion to the active metabolite from clopidogrel and vicagrel, a novel.anti-platelet agent, and support the drug design rationale in the view of the pharmacokinetics.Following intravenous administration to rats, vicagrel was rapidly converted to its thiolactone intermediate (2-oxo-clopidogrel), then to the active metabolite.The transformation efficiency of vicagrel to 2-oxo-clopidogrel was 94%, but only 13% of clopidogrel was converted to 2-oxo-clopidogrel.Compared to clopidogrel following oral administration to rats and beagle dogs at equal molar doses, vicagrel increased the exposure to 2-oxo-clopidogrel approximately 6-fold (58.6±10.2 vs.10.2±6.6μg·h/L in rats, 97.1±51.9 vs.16.1±3.3μg·h/L in dogs) and the.exposure to the active metabolite approximately 4-to 6-fold (59.0±18.8 vs.14.4±9.6μg·h/L in rats, 635.1±114.5 vs.99.0±10.3μg·h/L in dogs).The rapid and extensive conversion of vicagrel to the intermediate 2-oxo-clopidogrel by esterase instead of CYPs makes the novel pro-drug vicagrei a promising agent to prevent platelet aggregation and overcome clopidogrel resistance and high inter-individual variability due to CYP2C 19 polymorphism.