| Objective: To study the effects of low,middle and high dose atorvastatin combined with clopidogrel on the pharmacodynamics and pharmacokinetics of clopidogrel in rats.To evaluate the rationality of combined use of atorvastatin and clopidogrel in order to provide reference for the application of anti platelet drugs in Department of Cardiology.Methods: The length and wet weight of thrombus in rat was observed by in vitro experiment,the platelet aggregation was induced by ADP about the low,middle and high dose atorvastatin(2 mg·kg-1,4 mg·kg-1 g,8 mg·kg-1)combined with clopidogrel(6.25mg·kg-1);and Blood clots instrument was used to determine the effect of prothrombin time?PT?,activated partial thromboplastin time?APTT?,thrombin time?TT?,and fibrinogen?FIB?content.The bleeding time and coagulation time in mice about the low,middle and high dose atorvastatin(4.11mg·kg-1?8.22mg·kg-1?16.44mg·kg-1)combined with clopidogrel(15.41mg·kg-1)was detected by tail cutting method,capillary glass tube method and slide method.After administration in rats,low-,medium-and high-dose atorvastatin(2 mg·kg-1,4mg·kg-1,8 mg·kg-1)was measured by high performance liquid chromatography?HPLC?.Effect of clopidogrel(6.25 mg/kg-1)on clopidogrel carboxylate?SR26334?concentration.Collected the cases admitted to Department of Cardiology were treated with different doses of atorvastatin combined with clopidogrel in Yichun People's Hospital from September 2016 to September 2017 through the hospital electronic medical record system and analyse the rationality of the clinical application.Results: Compared with the clopidogrel alone group?thrombus length 4.230±2.130 cm,weight 0.136±0.056 g,platelet maximum aggregation rate 22.81±9.55%?,mid-dose atorvastatin(4 mg·kg-1)had enhanced chlorine Antipyretic and antiplatelet effects of pirigolide?thrombus length 3.311±1.791 cm,weight 0.051±0.044 g,maximum platelet aggregation rate 10.61±5.57%?,but high-dose atorvastatin(8mg·kg-1)inhibited Clopidogrel antithrombotic and antiplatelet effect?thrombus length 5.680±0.295 cm,weight 0.124±0.063 g,platelet maximal aggregation rate 28.23±12.66%?;clopidogrel alone and low and medium doses compared with saline group The PT,TT and APTT in atorvastatin group were significantly prolonged?P<0.05?.The FIB in the combination of low-and middle-dose atorvastatin and clopidogrel was significantly lower with statistical difference?P<0.05?;The TT of middle-dose atorvastatin combined with clopidogrel group was?32.09±0.65?,which was significantly longer than that of clopidogrel alone group?P<0.05?;middle-dose atorvastatin The FIB in combination with clopidogrel was?1.04±0.52?,which was significantly lower than that of clopidogrel alone,with statistical significance?P<0.05?.The clopidogrel carboxylate concentration(C=8.90±2.72 ng·dl-1)in the combination of high-dose atorvastatin and clopidogrel was significantly increased compared with the clopidogrel alone group?C=4.93±2.07?.The difference was statistically significant?P<0.05?.In the clopidogrel group alone,bleeding time was 625±365,?653±264?,?673±212?,and?649±275?for the combination of low,middle,and high doses of atorvastatin and clopidogrel,respectively.s,compared with the saline group,were significantly prolonged,the difference was statistically significant?P <0.05?;clopidogrel alone group,low,medium and dose atorvastatin combined with clopidogrel group clotting time They were?36±28?,?44±19?,and?37±12?s,respectively.Compared with the saline group,they were significantly prolonged.The difference was statistically significant?P<0.05?.The clotting times of low-and mid-dose atorvastatin combined with clopidogrel group were?101±51?,?105±35?,?97±39?,respectively,measured by capillary glass tube method.s,compared with the saline group,were significantly prolonged,the difference was statistically significant?P <0.05?.In the Department of Cardiology,September 2016 to September 2017,there were a total of 105 cases of atorvastatin combined with clopidogrel.Among them,70 were males and 35 were females,accounting for 66.67% and 33.33% of the total cases respectively;87 patients were over 50 years old,accounting for 82.86% of the total cases;atorvastatin?20mg?was used in 105 cases.There were two cases with clopidogrel?50 mg?,accounting for 1.90%;atorvastatin?20 mg?plus clopidogrel?75 mg?with 64,60.95%;atorvastatin?40 mg?plus clopidogrel?75 mg??19,18.1%?;atorvastatin?60 mg?plus clopidogrel?75 mg?1 case,0.95%;atorvastatin?80 mg?plus clopidogrel?75 mg?8 cases Accounted for 7.62%.Conclusion: This result suggests that mid-dose atorvastatin is beneficial to the antiplatelet and antithrombotic effects of clopidogrel,while high-dose atorvastatin competes with the clopidogrel metabolic process,resulting in an effect on clopidogrel Inhibition.The combination of low-and mid-dose atorvastatin with clopidogrel does not affect the metabolism of clopidogrel,but the combination of high-dose atorvastatin and clopidogrel competitively inhibits the metabolism of clopidogrel,thus clopidogrel The antithrombotic and antiplatelet effects were weakened,which was consistent with the high-dose atorvastatin combined with clopidogrel group in the first quarter to inhibit clopidogrel antithrombotic and antiplatelet effects.High-dose atorvastatin combined with clopidogrel prolonged clopidogrel hemorrhage in mice,but inhibited clopidogrel's clotting effect,indicating that atorvastatin will inhibit clopidogrel's antithrombotic effect with increasing dose Without attenuating the adverse effects of bleeding.The combination of clinical atorvastatin and clopidogrel is more common,and the dose of atorvastatin when combined is from 1080 mg.It is recommended to reduce the dose of atorvastatin when combined,and to prevent the high atorvastatin inhibit clopidogrel antithrombotic effect,reduce the incidence of cardiovascular and cerebrovascular adverse events. |
PDF Full Text Request