抗癫痫药拉莫三嗪的血药浓度测定及动物的药代动力学研究

MONITOR OF LAMOTRIGINE IN PATIENTS SUFFERING FROM EPILEPTIC AND ITS PHARMACOKINETICS STUDY IN RABBITS

目的 :测定血清中拉莫三嗪的浓度及动物的药代动力学研究。方法 :采用HPLC ,以苯乙酮为内标 ,甲醇 KH2 PO4 ( 0 .0 5mol·L 1,pH 3.8)为流动相 ,经YWGODS柱 ( 2 0 0mm× 3.6mm)分离 ,30 5nm波长的二极管阵列检测器检测。取家兔以 2 5mg·kg 1经胃给药 ,设定时间抽血 ,测定动物药代动力学参数。结果 :浓度在 0 .2 5～ 5 0 μg·ml 1范围内线性良好 (r=0 .9998) ,平均回收率为 93 78%± 2 6 6 % ,日内RSD和日间RSD分别为 2 4% (n =9)和 5 3% (n =5 )。动物血药浓度 时间曲线经 3p87药代动力学程序包拟合 ,结果Cmax=9.34 μg·ml 1,t1/ 2 (ke) =8.78h ,CL/f(s)为0 .6 9L·h 1。结论

OBJECTIVE:To monitor serum concentrations of lamotrigine in the treating of epileptic patients and study the pharmcokinetics in rabbits.METHODS:Lamotrigine concentrations in serum were assayed by HPLC with YWG ODS as column and detected at 305 nm.Pharmcokinetics were studied after a single dose 25 mg·kg 1 ig to 3 rabbits.The parameters were computed with 3p87 program.RESULTS:The linear range was from 0.25 to 50 μg·ml 1 ( r =0.9998)and the average recovery was 93.78%±2.66% in the methodology.The concentration time curve of lamotrigine in rabbits fitted to two compartment model,which C max was 9.34 μg·ml 1 , t 1/2 (Ke) was 8.78 hours and CL/f(s) was 0.69 mg·h 1 ·μg 1 .CONCLUSION:The methods are rapid,accurate and can be used as routine test in the use of lamotrigine.