The Effective Concentration Range Of Lamotrigine In Epilepsy Patients

Part one:A high performance liquid chromatography method was established for the determination of lamotrigine unbound concentration in plasmaObjectiveA high performance liquid chromatography method for the determination of unbound concentration of lamotrigine in human plasma was established for patients with epilepsy.The correlation between unbound concentration and total concentration of lamotrigine and the effect of valproic acid on lamotrigine unbound concentration were investigated.MethodsA high performance liquid chromatography method for determining the unbound concentration of lamotrigine in human plasma was established and validated using a plasma-containing plasma sample.Phenacetin was used as internal standard,and the plasma was extracted by diethyl ether.The high performance liquid chromatography method was performed on the C18 column.The mobile phase consisted of acetonitrile-0.05 mol/L biphosphate sodium?25:75,pH 4.5?.The flow rate was 1.0 mL/min and the column temperature was kept at 25?.The detecting wavelength was set at 220nm.The method was inspected in the aspects of specificity,lower limit of quantification,accuracy and precision,recovery rate and stability.A total of 73 patients with epilepsy who received lamotrigine treatment at Shengjing Hospital affiliated to China Medical University from February 2017 to April 2017 were enrolled.SPSS 22.0 statistical software was used analyze.ResultsThe linear range of unbound lamotrigine were from 0.20 to 10.00?g/mL(y=12.42×10^-2 c+5.47×10^-3,R²=0.9992),show a good linear relationship.The intra and inter-day precision were both less than 15%.The extraction recovery rate is greater than 85%.The average unbound concentration was 0.97?0.80,1.14??g/mL of73 patients.Comparing the unbound concentration and total concentration of lamotrigine,the results showed a certain correlation?R²=0.8624?.In patients with valproic acid,the unbound concentration of lamotrigine was significantly higher than that of patients taking lamotrigine alone.Valproic acid increased the unbound and total concentrations of lamotrigine by 145.5%and 148.4%,respectively.ConclusionA method for determining the unbound concentration of lamotrigine was established.The method was simple,rapid and sensitive.The unbound concentration of lamotrigine was related to the total concentration.The combination of valproic acid increased the unbound concentration of lamotrigine.Part two: Study on effective therapeutic concentration of lamotrigine in epilepsy populations Objective The aim of this study was to establish a range of effective concentrations of lamotrigine in different epilepsy populations in China to guide rational clinical use of lamotrigine,so as to obtain the maximum curative effect with the minimum dose,ensure the effectiveness and safety of clinical use,and achieve individualized treatment of patients.Methods A total of 299 cases of epilepsy patients who received lamotrigine monotherapy in Shengjing hospital affiliated to China medical university from August 2016 to July 2018 were collected.According to the literature reports,the patients were divided into childhood,adolescence and adulthood.Samples were collected after patients received lamotrigine steady state plasma concentration,and the plasma concentration of lamotrigine was determined by high performance liquid chromatography.Efficacy and safety were evaluated according to patient observation indexes.SPSS 22.0 software was used for analysis of the data.By monitoring the LTG blood concentration and the seizure reduction rate,the ROC curve was used to determine the lower limit of the effective concentration range of LTG and the concentration-effect curve was used to determine the upper limit of the effective concentration range of LTG by clinical efficacy.Results In the ROC curve evaluation,the diagnostic curve with the concentration of lamotrigine as the predictor was higher than the diagnostic curve with the dose as the predictor,showing a higher prediction accuracy.According to the optimal cut-off point of the ROC curve,the lower limits of the effective concentration range in the childhood,adolescence and adulthood were 3.99 ?g/m L,2.67 ?g/m L and 1.88 ?g/m L,respectively.According to the concentration-effect curve,the upper limits of the effective concentration range in the childhood and adolescence were 8.97 ?g/m L and 8.56 ?g/m L,respectively.Conclusion Correlation between blood concentration of lamotrigine and clinical efficacy by clinical follow-up observation,and identified the effective concentration range of LTG trough concentrations in childhood 3.99-8.97 ?g/m L and adolescence 2.67-8.56 ?g/m L.The effective concentration range in adulthood is a concentration above 1.88 ?g/m L,and the upper margin of LTG trough level is the plasma trough concentration at the minimum dose at which seizures can be controlled.