文拉法辛联合长春西汀在大鼠体内的药代动力学研究

Pharmacokinetic study of venlafaxine combined with vinpocetine in rats

目的研究文拉法辛(VEN)联合长春西汀(VIN)在大鼠体内的药代动力学,以考察两者的相互作用。方法将健康雄性SD大鼠随机分为VEN组(13.5 mg/kg)、VIN组(1.8 mg/kg)和VEN+VIN组(13.5 mg/kg VEN+1.8 mg/kg VIN),每组6只。给药前,各组大鼠禁食不禁水12 h,一次性灌胃给予相应药物。各组大鼠于给药后不同时间点经眼眶静脉丛采血。将血浆样品预处理后(以多潘立酮为内标),采用液相色谱-串联质谱(LC-MS/MS)法检测血浆中VEN、VEN活性代谢产物O-去甲文拉法辛(ODV)、VIN活性代谢产物阿朴长春胺酸(AVA)的浓度。采用DAS2.0软件计算VEN、ODV、AVA的药代动力学参数并进行组间比较。结果与VEN组比较,VEN+VIN组大鼠血浆中VEN、ODV的药代动力学参数c_(max)、AUC_(0-t)、AUC_(0-∞)、MRT_(0-t)(VEN除外)、MRT_(0-∞)(VEN除外)均显著增大,CL/F、V_(z)/F均显著减小(P<0.05或P<0.01)。与VIN组比较,VEN+VIN组大鼠血浆中AVA的各项药代动力学参数差异均无统计学意义(P>0.05)。结论VEN和VIN联用后,VIN可通过增大VEN、ODV吸收程度、减慢两者消除,影响VEN的代谢。

OBJECTIVE To study the pharmacokinetics of venlafaxine(VEN)combined with vinpocetine(VIN)in rats,and to investigate the interaction between them.METHODS Healthy male SD rats were randomly divided into VEN group(13.5 mg/kg),VIN group(1.8 mg/kg)and VEN+VIN group(13.5 mg/kg VEN+1.8 mg/kg VIN),with 6 rats in each group.Before administration,rats in each group fasted but didn’t deprived of water for 12 hours,and were given corresponding drugs intragastrically at one time.Blood was collected from rats in each group through orbital venous plexus at different time points after administration.After plasma sample was pretreated(domperidone as internal standard),LC-MS/MS method was adopted to determine the concentration of VEN,active metabolite O-desmethylvenlafaxine of VEN(ODV)and active metabolite apovinblastic acid of VIN(AVA)in plasma.DAS2.0 software was used to calculate and compare the pharmacokinetic parameters of VEN,ODV and AVA.RESULTS Compared with VEN group,the pharmacokinetic parameters c_(max),AUC_(0-t),AUC_(0-∞),MRT_(0-t)(except for VEN),MRT_(0-∞)(except for VEN)of VEN and ODV in VEN+VIN group were increased significantly,while CL/F and V_(z)/F were decreased significantly(P<0.05 or P<0.01).Compared with VIN group,there was no statistical difference in the pharmacokinetic parameters of AVA in rat plasma of VEN+VIN group(P>0.05).CONCLUSIONS After the combination of VEN and VIN,VIN can affect the metabolism of VEN by increasing the absorption of VEN and ODV and slowing down their elimination.