Pharmacokinetic study of venlafaxine combined with vinpocetine in rats / 中国药房

ABSTRACT

OBJECTIVE To study the pharm acokinetics 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. DAS 2.0 software was used to calculate and compare the pharmacokinetic parameters of VEN ，ODV and AVA. RESULTS Compared with VEN group ，the pharmacokinetic parameters cmax，AUC0－t，AUC0－∞，MRT0－t（except for VEN），MRT0－∞（except for VEN ）of VEN and ODV in VEN+VIN group were increased significantly ，while CL/ F and Vz/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.