ABSTRACT
Objective To investigate the antiplatelet effects of candidate drug W1 when combined with omeprazole,respec?tively.Methods The experimental rats were randomly divided into 5 groups:control group,clopidogrel(10 mg/kg)group,clopido?grel(10 mg/kg)+omeprazole(80 mg/kg)group,W1(3 mg/kg)group,and W1(3 mg/kg)+omeprazole(80 mg/kg)group.Four hours after oral administration of the drugs,the rats were measured for their platelet aggregation rate;Western blot was used to deter?mine the protein expressions of P2Y12 receptor,P-Akt and P-Erk.Results For the platelet aggregation rate,compared with the con?trol group,the 4 groups decreased significantly(P<0.01);the platelet aggregation rate in the clopidogrel + omeprazole group in?creased significantly than that in the clopidogrel group(42% and 20.4%,respectively,P<0.01);the platelet aggregoction rate (30.9%)in W1+omeprazole group was significantly higher(P<0.01)than that in the W1 group(20.5%),which was lower than that in the clopidogrel+omeprazole group(P<0.01).For the protein expression detected by the western blotting,there were no signif?icant changes in the expression of P2Y12 receptor on the platelet surface,in the clopidogrel or W1 group in comparison with the clopi?dogrel+omeprazole or W1+omeprazole group,respectively,while the phosphorylation level of Akt and Erk was up-regulated in the clopidogrel+omeprazole or W1+omeprazole group compared with the clopidogrel or W1 group,and the up-ragulatory effect of omepra?zole was weaker in the W1+omeprazole group than that in the clopidogrel+omeprazole group. Conclusion Combined use of omepra?zole could inhibit the antiplatelet activities of clopidogrel or W1,with the inhibitory effect weaker in W1 group than in clopidogrel group,suggesting that the risk for the combination of omeprazole with W1 is likely less than that for the combination with clopidogrel.