Relationship Between Epileptic Seizures During Pregnancy And The Change Of Pharmacokinetics Of Levetiracetam(LEV) And Lamotrigine(LTG)

Objective: In order to guide the rational treatment of epilepsy during pregnancy,the characteristic of apparent clearance,blood concentration,dose and the control effect of epilepsy during pregnancy were collected when we using single or multi-drug therapy including Lamotrigine and Levetiracetam to treat epilepsy during pregnancy.Method: We collected the consecutive pregnant women with epileptic cases who were treated in the epilepsy clinic of Shengjing Hospital from January 2014 to December 2020,in order to analyze the apparent clearance,blood concentration,dose,as well as epileptic seizure during pregnancy of LTG and LEV.Result: 1.The apparent clearance of LEV and LTG monotherapy increased at all stages of pregnancy compared with the pre-pregnancy baseline level,especially in late pregnancy,and increased by 222.92%(P =0.020)and 267.91%(P =0.016),respectively.The blood concentration decreased at all stages of pregnancy compared with the pre-pregnancy baseline level,especially in mid pregnancy,and increased by 52.38%(p=0.008)and64.78%(p=0.009),respectively.The variation trend and peak of blood concentration and clearance of multi-drug therapy including LEV and LTG were the same as that of monotherapy,but the overall variation trend was slightly lower than that of monotherapy.2.The dose of LEV and LTG monotherapy increased at all stages of pregnancy compared with the pre-pregnancy baseline level,especially in late pregnancy,and increased by110.85%(p=0.001)and 89.06%(p=0.001),respectively.3.The maximum frequency of seizures of LEV and LTG monotherapy occurred in mid pregnancy,but there was no statistical difference in seizure control between the two regiments(P=0.733).4.In the treatment regimens that included LEV and LTG,we found that the proportion of epileptic seizures after pregnancy was higher in patients with uncontrolled seizures before pregnancy than patients with seizures controlled before pregnancy(p=0.002,p=0.006).Conclusion: 1.The apparent clearance,blood concentration and dose of LTG and LEV monotherapy and multidrug therapy all changed significantly during pregnancy compared with the pre-pregnancy baseline level,which showed that the clearance rate and drug dosage increased,while the blood concentration decreased.2.Compared with LEV,LTG showed significant changes in the apparent clearance,blood concentration and dose at all stages of pregnancy,but there was no statistical difference in epileptic seizure control between the two regiments.3.The proportion of epileptic seizures after pregnancy was higher in patients with uncontrolled seizures before pregnancy than patients with seizures controlled before pregnancy.Therefore,the premise of reducing epileptic seizures during pregnancy is to do well in the management and counseling of epilepsy before pregnancy.4.The variation trend of epileptic seizure during pregnancy was the same as that of blood drug concentration.In order to avoid epileptic seizures during pregnancy,blood concentration monitoring should be carried out in women with epilepsy during the whole pregnancy.