The Safety Study Of Sodium Valproate Combined With Carbapenem

Objective:To analyze the safety of sodium valproate combined with carbapenem,and discuss its solutions.Methods:?A total of 307 inpatients with sodium valproate were collected,the plasma concentration of sodium valproate was detected by chemiluminescent immunoassay,the influence of different factors on the plasma concentration were discussed and multiple regression models were used to analyze.?We collected another 20 cases of sodium valproate combined with meropenem,monitored and analyzed the plasma concentration of sodium valproate before,in treatment and after stopping combination,and paid close attention to epilepsy related symptoms.And we predicted the plasma concentration after sodium valproate combined with meropenem by support vector machine model.?Design solutions for combined cases:The dosage of sodium valproate was increased in 4 cases,the drugs were replaced in 8 cases,the change situation of plasma concentration of sodium valproate was monitored and the epilepsy related symptoms was observed.?6 cases of sodium valproate combined with imipenem cilastatin were collected to study whether the change of plasma concentration of sodium valproate was similar to that of meropenem.Results:?The average plasma concentration of sodium valproate was 45.1 ±23.5?g/mL in 307 inpatients collected,which was slightly lower than effective treatment concentration(50 ?g/mL?100 ?g/mL).The regression equation was established by using multivariate regression model:Y=8.833+2.365X1+0.62X2+0.446 X3,the influence of average body daily dosage,age and dosage form on plasma concentration of sodium valproate ranked the top three.? 20 cases of sodium valproate combined with meropenem were analyzed,meropenem resulted in an average decrease of 83.2±7.7%in the plasma concentration of sodium valproate,the plasma concentration decreased at 1.2±0.4 days after combination,it decreased to a stable low value after 4.6±2.1 days,the plasma concentration needed an average of 9.4±3.5 days to recover after meropenem was discontinued,40%of the patients appeared epilepsy related symptoms.The support vector machine model could predict the plasma concentration of sodium valproate combined with meropenem,the average relative error was 14.9±7.8%,root mean square error was RMSE=1.1845,residual was small,the prediction effect was better.?The results of the two drug adjustment methods:a)The daily dosage of sodium valproate was increased by 75.0±28.9%on average,the plasma concentration was increased by 9.3±9.3%only,there was no increase phenomenon comparatively,the incidence rate of epilepsy was 50%,it was the same as before;b)Sodium valproate was replaced by carbamazepine or levetiracetam,meropenem was replaced by cefoperazone sulbactam,there was no epilepsy related symptoms in the former and no decrease in plasma concentration in the latter.?The average plasma concentration of 3 cases was decreased by 71.7±5.3%in cases of sodium valproate combined with imipenem cilastatin,and the plasma concentration did not increase as compared with increasing the dosage of sodium valproate in the other 3 cases.Conclusion:The combination of sodium valproate and carbapenem can lead to a significant decrease in the plasma concentration of sodium valproate,it should be avoided as far as possible,and it can not be solved by increasing the dosage of sodium valproate,but sodium valproate can be replaced by carbamazepine or levetiracetam,carbapenem can be replaced by cefoperazone sulbactam to achieve the purpose of effective treatment of epilepsy and infection.