| Objective To explore the optimal dose and interval dose of aspirin,offering experiment proof for clinical rational use,we detected the plasma concentrations of salicylic acid and changes of platelet aggregation rate(PAG) in SD rats after taking different doses of aspirin in different time,by using high performance liquid chromatograph and platelet aggregation equipment respectively.Methods 35 SD rats were randomly divided into five groups,the control group and four different aspirin groups(group 1 with 10mg.Kg-1.d-1 qod,group 2 with 10mg.Kg-1.d-1 qd,group 3 with 30mg.Kg-1.d-1 qod,and group 4 with 30mg.Kg-1.d-1 qd).After giving aspirin 7 time serially,Blood was sampled before giving aspirin for the 8,9 and 10 time,then drew blood(0.5,1.0,1.5,1.75,2.0,3.0,4.0,5.0,7.0,9.5,12.0h,11 time points) from orbital vein.The plasma concentrations of salicylic acid was detected by using high performance liquid chromatograph under standard chromatographic condition,preparing standard curve and carrying out the test of recovery and precision at the same time.After the pharmacokinetics research,blood was sampled from abdominal aorta by anesthetizing all the rats,then platelet aggregation rate was measured on platelet aggregation equipment using arachidonic acid(500mg.l-1) and ADP(10μmol.1-1) as platelet aggregation inductor respectively.Results①The results of pharmacokinetics were the following:the plasma concentrations of salicylic acid on the group 1 was not detected at last,while the comparison of the plasma concentrations of salicylic acid between group 2 and group 3 having no statistical significance(P＞0.05),but all having statistical significance(P＜0.01) when compared with group 4 respectively.②The results of pharmacodynamics were the following:the disparity of platelet aggregation rate between all aspirin groups and control group have statistical significance(P＜0.05),no matter using arachidonic acid or ADP as platelet aggregation inductor;except for having no statistical significance(P＞0.05) between group 2 and group 3,the platelet aggregation rate between all other aspirin groups have statistical significance(P＜0.01).Conclusions Both the results of pharmacokinetics and pharmacodynamics show that small dose of aspirin administering once a day(100mg,qd) and large dose of aspirin administering on alternate days(300mg,qod) could inhibit platelet aggregation equally. Objective To evaluate the effectiveness and safety of clopidogrel plus aspirin on patients with ST-segment elevation acute myocardial infarction(AMI).Methods We searched for randomized controlled trials(RCTs) and quasi-RCTs in the following electronic databases:Pubmed(1998-2007.10),EMBASE(1998-2007.10), The Cochrane library(Issue 3,2007),CBM(1998～2007.10),CNKI(1998～2007.10), VIP(1998～2007.10),and WanFang(1998-2007.10).Quality assessment and data extraction were conducted by two reviewers independently,according to quality criteria (randomization procedure,allocation concealment and blinding) Cochrane Reviewer's Handbook,disagreement were resolved through discussion.All data were analyzed by using Review Manager4.2.If there were heterogeneity among these studies,we did statistics analysis by using random effect model;and if there were no heterogeneity,we did statistics analysis by using fixed effect model.The relative risk(RR) and 95% confidence interval(CI) were used for reporting those data.Results Ten studies involving a total of 52 433 participants met the inclusion criteria, with 4 RCTs and 6 CCTs.The outcomes of Meta-analysis implied that:①Compared with aspirin alone,clopidogrel plus aspirin could reduce the incidence of death caused by any reasons(RR0.92,95%CI-0.86 to 0.97),reinfarction(RR0.81,95%CI-0.73 to 0.89),stroke(RR0.81,95%CI-0.68 to 0.96),infarction angina(RR0.38,95%CI-0.20 to 0.71)and incoronary thrombus(RR0.84,95%CI-0.77 to 0.90).②There were no significant differences between the two groups in reducing combination of death, reinfarction,or stroke,heart failure and increasing TIMI myocardial-perfusion grade of 3(P＞0.5).③Safety:There were no significant differences between the two groups (RR1.10,95%CI-0.92 to 1.33).Conclusion Clopidogrel plus aspirin have good effects on patients with ST-segment elevation acute myocardial infarction,reducing death caused by any reasons, reinfarction,stroke,reinfarction angina,and incoronary thrombus,not increasing bleeding,but having no effect on death,reinfarction,or stroke,heart failure and TIMI myocardial-perfusion grade of 3.
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