难治性癫痫患者脑组织致痫灶与灶旁组织药物浓度的比较研究  

Comparative Study on Concentrations of Antiepileptic Drugs in Epileptogenic Focus and Adjacent Tissue in Patients with Intractable Epilepsy

作　　者：沈江华[1] 姜德春[1] 王育琴[1] 

机构地区：[1]首都医科大学宣武医院药剂科,北京100053

出　　处：《中国药学杂志》2011年第10期774-777,共4页Chinese Pharmaceutical Journal

摘　　要：目的通过比较难治性癫痫（IE）患者脑内致痫灶、灶旁组织的药物浓度的差异,促进阐明IE的耐药机制。方法收集自2007年4月~2009年3月在首都医科大学宣武医院功能神经外科行＂致痫灶切除术＂的IE患者。用高效液相色谱法（HPLC）测定脑组织致痫灶和灶旁组织药物浓度,比较其差异。所有患者均在术前获得知情同意。结果①共收集到23例患者的脑组织,分别服用苯巴比妥（PB）、苯妥英钠（PHT）、卡马西平（CBZ）和拉莫三嗪（LTG）,将致痫灶和灶旁组织用电生理的方法进行分离,用于脑组织药物浓度的测定。剔除3例,剩余20例,包括PB 4例,CBZ 16例。②20例患者脑组织致痫灶的平均药物浓度为（1.83±0.39）μg.mL-1,灶旁组织的平均药物浓度为（2.11±0.45）μg.mL-1,采用配对t检验的方法,P=0.000〈0.05,结果有统计学差异,致痫灶的药物浓度低于灶旁组织。分别观察PB组与CBZ组的结果,得出一致性结论。结论本试验的前续研究已经证实P糖蛋白（P-gp）在脑组织的致痫灶中比灶旁组织表达量多,且本试验所选药物均是P-gp的底物,在P-gp表达产物外排泵的作用下,使致痫灶中的药物浓度低于灶旁组织,导致了患者的耐药。OBJECTIVE To clarify the mechanism of drug resistance by comparing the antiepileptic drug concentration in epileptic foci and lesion adjacent tissue.METHODS Patients diagnosed with intractable epilepsy and underwent excision operation of epileptic foci in functional neurosurgery of Xuanwu Hospital of Capital Medical University were collected from April 2007 to March 2009.The drug concentration in the intractable epileptic patients was determined by high performance liquid chromatography.All patients provided informed consent before surgery.RESULTS Twenty-three cases who took phenobarbital（PB）,phenytoin（PHT）,carbamazepine（CBZ） or lamotrigine（LTG） before surgery,were collected.All epileptic foci and lesion adjacent tissues were distinguished by nerve electrophysiological method,and used for drug concentration determination.Three cases were excluded.The remaining cases included 4 cases of PB and 16 cases of CBZ.There were 20 patients in this study.The average drug concentration in epileptic foci was（1.83±0.39）μg·mL-1.The average drug concentration in lesion adjacent tissue was（2.11±0.45）μg·mL-1,SPSS statistical analysis result was statistically significant.The drug concentrations in epileptic foci tissue were lower than that in the lesion.The same results were shown in groups of PB and CBZ.CONCLUSION Previous study has showed that P-gp expression in epileptic foci is significantly higher than that in lesion adjacent tissue.All the drugs included in this study（PB,CBZ,PHT and LTG）are substrates of P-gp.We conclude that the higher expression of P-gp in epileptic foci results in lower drug concentration than that in lesion adjacent tissue.

关 键 词：难治性癫痫 脑组织 药物浓度 高效液相色谱 耐药机制 

分 类 号：R969.11[医药卫生—药理学]