妊娠期癫痫患者左乙拉西坦药动学行为变化

目的：系统研究左乙拉西坦（levetiracetam，LEV）在妊娠期癫痫患者体内药动学行为变化，并探究基于LEV血药浓度监测，调整妊娠期癫痫患者的给药方案。方法：回顾性收集2017年1月至2021年7月于中国医科大学附属盛京医院就诊并进行LEV血药浓度监测的妊娠期癫痫患者的临床病历资料，计算孕前至产后LEV的表观清除率（CL），分析妊娠期癫痫患者LEV的给药方案，并探究妊娠期合并用药对LEV体内药动学行为的影响。结果：对17例单用LEV治疗的妊娠期癫痫患者138次血药浓度监测数据的回顾性分析表明，妊娠期LEV的CL显著增加，与孕前基线相比，在妊娠早期、中期及晚期分别增加了86.39%（P<0.01）、148.30%（P<0.01）和134.69%（P<0.01），分娩后迅速下降，于产后6周左右恢复至孕前水平。不同妊娠时期LEV给药剂量存在差异，妊娠中、晚期给药剂量较孕前分别增加了44.93%（P<0.01）和96.07%（P<0.01）。妊娠期合用具酶诱导作用的抗癫痫药能够诱导LEV代谢，使LEV的CL增加。结论：妊娠期癫痫患者LEV体内药动学行为变化显著，其CL于妊娠中期达到峰值，分娩后迅速降低。与具酶诱导作用的抗癫痫药合用会增加LEV的CL。定期监测LEV血药浓度可为妊娠期癫痫患者的药物治疗管理提供指导。

Pharmacokinetic changes of levetiracetam in patients with epilepsy during pregnancy

OBJECTIVE To systematically study the pharmacokinetic changes of levetiracetam (LEV) in patients with epilepsy during pregnancy, and to explore the adjustment of dosing regimen during pregnancy based on the monitoring of LEV serum concentration.METHODS The clinical data of patients with epilepsy during pregnancy who were admitted to Shengjing Hospital of China Medical University from January 2017 to July 2021 and had regular therapeutic drug monitoring of LEV were collected retrospectively.The apparent clearance (CL) was calculated from preconception to postpartum.The dosing regimen of LEV in patients with epilepsy during pregnancy was analyzed, and the effects of concomitant antiepileptic drugs (AEDs) on the pharmacokinetics of LEV during pregnancy were explored.RESULTS A total of 138 blood samples were collected from 17 patients with epilepsy during pregnancy treated with LEV alone.The CL of LEV during pregnancy increased significantly, increased by 86.39% (P<0.01) during the first trimester, 148.30% (P<0.01) during the second trimester and 134.69% (P<0.01) during the third trimester compared with the pre-pregnancy levels.The CL decreased rapidly after delivery and returned to the pre-pregnancy levels about 6 weeks after delivery.There were differences in the dose of LEV in different pregnancy periods.The LEV dose in the second and third pregnancy was significantly higher than that in pre-pregnancy, increased by 44.93% (P<0.01) and 96.07% (P<0.01) respectively.The concomitant medication with enzyme-induced AEDs can induce LEV metabolism and increase its CL.CONCLUSION The pharmacokinetic behavior of LEV during pregnancy changed, and its CL reached the peak in the second trimester and decreased rapidly after delivery.When concomitant with enzyme-induced AEDs, the CL of LEV would be increased.Regular monitoring of LEV serum concentration can provide guidance for drug treatment and management of patients with epilepsy during pregnancy.