癫痫患者拉莫三嗪治疗药物监测研究进展

Research Progress on Therapeutic Drug Monitoring of Lamotrigine for Epileptic Patients

目的为临床合理使用拉莫三嗪(LTG)提供参考。方法检索中国知网、万方、维普、PubMed、Web of Science数据库自建库起至2023年11月的LTG治疗药物监测相关文献,从治疗窗、药物代谢动力学(简称药动学)特征,特殊人群(妊娠期女性、儿童、老年人等)药动学特征及代谢酶相关基因多态性对血药浓度的影响等方面,总结LTG治疗药物监测研究进展。结果LTG是治疗癫痫发作和双相情感障碍的药物,临床应用时需参考最新治疗窗;临床监测样本以血浆为主,头发和唾液也可作为非入侵样本;血药浓度检测的主要方法为液相色谱法,荧光光谱法和电化学传感器正逐渐被应用。LTG生物利用度约为98%,蛋白质结合率约为55%,达峰时间不受给药剂量限制;在与其他药物联用时要注意调整剂量。有潜在生育能力的癫痫女性用药首选LTG,用于老年癫痫时更适用于新发患者,对于癫痫患儿应重点监测血药浓度,以避免发生不良反应。尿苷5'-二磷酸-葡萄糖醛酸糖基转移酶是参与LTG代谢的主要酶,其相关基因的多态性也是血药浓度的重要影响因素。结论应采用合适的样本和方法检测LTG血药浓度,并关注不同人群及不同基因型,以预防严重不良反应的发生。

Objective To provide a reference for the rational use of lamotrigine(LTG)in clinical practice.Methods Literature related to the therapeutic drug monitoring(TDM)of LTG in the CNKI,WanFang,VIP,PubMed and Web of Science from the inception of each database to November 2023 were searched.The research progress of TDM of LTG was summarized from the therapeutic window,pharmacokinetic characteristics,pharmacokinetic characteristics of special populations(pregnant women,children,elderly),and effect of metabolic enzyme-related gene polymorphisms on the plasma concentration.Results LTG is a drug for epilepsy and bipolar disorder,and its clinical application needs to be based on the latest therapeutic window.The clinical monitoring sample of LTG is mainly plasma,hair and saliva are also non-invasive samples.The detection method of LTG concentration is mainly liquid chromatography,fluorescence spectroscopy and electrochemical sensor are gradually being applied.The bioavailability of LTG is about 98%,the protein binding rate is about 55%,and the time to peak is not limited by the dosage of the drug.Pay attention to adjusting the dosage of LTG when used in combination with other drugs.LTG is priority for epileptic women with potential fertility,it is more suitable for newly-diagnosed epileptic patients for elderly,and plasma concentration should be monitored for epileptic children to avoid adverse reactions.Uridine 5'-diphosphate glucuronosyltransferases is the main enzyme involved in LTG metabolism,and the polymorphism of its related genes is an important factor affecting the plasma concentration.Conclusion We should detect LTG concentration through suitable samples and methods,pay attention to different populations and genotypes to prevent the occurrence of serious adverse reactions.