雷贝拉唑对大鼠体内稳态时氯吡格雷药动学的影响
Effect of Rabeprazole on Steady-State Pharmacokinetics of Clopidogrel in Rats
氯吡格雷 / 雷贝拉唑 / 奥美拉唑 / SR26334 / 药动学 / 药物相互作用 {{custom_keyword}} /
?To study the effect of rabeprazole on the steady-state pharmacokinetics of clopidogrel in rats. METHODS??Eighteen healthy SD rats were divided into three groups, which were intragastricly administered clopidogrel (30 mg·kg-1·d-1 ) / rabeprazole (8 mg·kg-1·d-1) + clopidogrel (30 mg·kg-1·d-1), omeprazole (8 mg·kg-1·d-1) + clopidogrel (30 mg·kg-1·d-1) respectively for 7 d. The plasma concentrations of the metabolite of clopidogrel, SR26334, were determined by HPLC-DAD. The pharmacokinetic parameters of SR26334 were obtained with statistical analysis by DAS 3.0. RESULTS??There was no significant difference between the single-drug group and the rabeprazole combination group in the main pharmacokinetic parameters of SR26334, such as AUC0-t, AUC0∞, MRT0-t, t1/2z, CLz/F, ρmax and ρss (P>0.05), except that the tmax significantly decreased from (1.17±0.41) h in the single-drug group to (0.58±0.20) h in the combination group (P<0.01). Compared with single-drug group, the AUC0-t and AUC0∞of the omeprazole combination group increased for about 20% (P<0.05), MRT0-t significantly prolonged (P<0.01), and CLz/F decreased for about 20% (P<0.05). CONCLUSION??Long-term combinaton treatment with rabeprazole can accelerate the in vivo metabolism of clopidogrel to SR26334 / but there is no significant influence on the degree of metabolism. {{custom_keyword}} /
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