Effect of oxacetam on pharmacokinetics of Nimodipine in rats
Objective:To establish a UPLC method for the determination of Nimodipine in plasma and to study the effect of Oxacetam on the pharmacokinetics of Nimodipine in rats.Methods:Rats were randomly divided into Nimodipine group(control group)and Oxacetam combined with Nimodipine group(combined group),with 6 rats in each group.The rats in the control group were gavaged with normal saline,and the rats in the combined group were gavaged with Oxacetam 200 mg·kg-1 for 7 consecutive days.On the 7th day after administration,fasting can't help but cause dehydration,on the 8th day,after routine administration,both groups were intragaxed with 20 mg·kg-1 Nimodipine,and blood was collected at different points of time.The content of Nimodipine in plasma was determined by UPLC method.The pharmacokinetic parameters were analyzed by DAS 2.0 pharmacokinetic software,and the pharmacokinetic parametric statistics were analyzed by SPSS 26.0 statistical software.Results:The linear relationship between Nimodipine content in plasma and its peak area was good in the concentration range of 50-5 000 mg·mL-1,Ŷ = 26.061X-307.974,R2 = 0.991.Intra-day precision was 1.80%-3.90%;Inter-day precision was 2.69%-12.72%;The recoveries were 83.53%-87.52%;thus specificity and stability meet the requirements.Pharmacokinetic parameters showed that compared with the control group,AUC(0-24)and Cmax were significantly increased in the combined group,while Tmax and Vz/F and were significantly decreased(P<0.05).Conclusion:The UPLC method established in this study for the determination of nimodipine in rat plasma has high sensitivity,good stability,and simple operation,which can be used for the determination and pharmacokinetics research of nimodipine in rat plasma,and Oxacetam can affect the pharmacokinetics of Nimodipine.Oxacetam can accelerate the absorption rate of Nimodipine,increase the bioavailability of Nimodipine,accelerate the metabolism of Nimodipine in rats,and shorten its action time in vivo.