氟桂利嗪抗癫痫及逆转难治性癫痫病人多药耐受基因的表达

Flunarizine: anticonvulsant activity and reversing overexpresion of P-glycoprotein-multidrug resistance gene in treatment of refractory epileptic patients

目的 :了解氟桂利嗪对多药耐受基因 1(MDR 1)表达阴性或阳性癫痫病人的抗癫痫作用及其逆转MDR 1表达的可能性。方法 :54例病人随机分成 2组。实验组用免疫组化法测定P糖蛋白(P gp) ,加用氟桂利嗪 5～ 10mg ,po ,qn ,2wk随访 1次 ,6～ 8wk后评价临床疗效 ,发作减少 50 %者为有效。用药前P gp阳性有效者同时复查P gp。对照组加用安慰剂同步观察。结果 :P gp阳性组的2 2例病人中有效 14例 ,阴性组 12例中有效 2例 ,对照组有效 4例。P gp阳性有效的 11例完成了P gp复查 ,其中 10例病人的P gp表达下降 50 %以上。氟桂利嗪的不良反应发生率为 2 3 %。结论 :氟桂利嗪辅助治疗有效 ,其抗癫痫机制可能与逆转P gp表达有关。

AIM:To evaluate the therapeutic effect of flunarizine in the treatment of the epileptic patients with or without the overexpresion of P glycorprotein (P gp), a produce of multiple drug resistance gene 1 and study the probable of flunarizine reversing P gp. METHODS:Fifty four patients with intractable epilepsy were divided into 2 groups after recording the seizure frequency per day for 6 8 wk. In the experimental group, after 5 mL of the venous blood was collected in each of the patients and the P gp were investigated with the method of the immunocytochemistry, 34 patients with intractable epilepsy (M 20, F 14; age 24 a± s 12 a) received flunarizine 5-10 mg, po , qn, for 6-8 wk, as an add on antiepileptic drug. Other similar 20 refractory epileptic patients(M 12, F 8; age 26 a± s 9 a)received placebo(amino acid co) for 6-8 wk. It was effective if the seizure frequency reduced 50 %. The effective patients with the P gp were to reexamine the P gp with the same method in wk 6-8. RESULTS: Fourteen of 22 patients with the P gp and 2 of 12 patients without P gp were effective. The effective rate of control group with placebo was 20 %(4/20). The levels of the P gp of 10 patients in the reexamined 11 patients reduced over 50 %. The rate of adverse reaction was 23 %, mainly associated with dizziness and drowsiness, but was mild. CONCLUSION: Flunarizine is effective, as add on therapy in intractable epilepsy with P gp. Adverse reactions are mild. The anticonvulsant mechanism of flunarizine may involve in reversing of P gp.