雷替曲塞在大鼠血浆和脑组织中的分布研究

Distribution of raltitrexed in plasma and brain tissue of rats

目的研究雷替曲塞静脉注射后在大鼠血浆和脑组织中的分布。方法采用HPLC法测定雷替曲塞2.5 mg.kg-1尾静脉注射后大鼠血浆和脑组织匀浆中的雷替曲塞浓度,计算药代动力学参数并比较评价。结果雷替曲塞在大鼠血浆及脑组织中的Tmax均为5 min,而Cmax分别为(12381.79±4515.83)ng.ml-1和(219.48±53.52)ng.ml-1,ROC曲线下面积(AUC)分别为(750 983.94±2 635.87)ng.min-1.ml-1和(962.25±147.18)ng.min-1.ml-1,血浆中Cmax和AUC显著高于脑组织中,差异具有统计学意义(P<0.01)。雷替曲塞在血浆中t1/2为(142.7±39.1)h。结论雷替曲塞静脉注射后能迅速分布到有关器官和组织,但不易透过血脑屏障。雷替曲塞在体内代谢缓慢,能较长时间维持有效的血药浓度。

Objective To study the distributions of raltitrexed in blood plasma and brain tissues of rats after caudal intravenous in- jection. Methods The concentrations of rahitrexed in plasma and brain tissues were detected by HPLC after raltitrexed intravenous injection in the dosage of 2.5 mg ~ kg- ~ and the pharmacokinetic parameters were calculated and analysed. Results Tma of raltitrexed in blood plasma and brain tissues of rats was both 5rain. Cmax was （12 381.79 ± 4 515.83） ng· ml-1 and （219.48 ± 53.52）ng· ml ; AUC was （750 983.94 ± 2 635.87 ） ng· min - l · ml - 1 and （962.25 ± 147.18 ） ng· min - 1 . ml -1. Cmax and AUC in blood plasma were all higher than those in brain tissues, and there was significant difference （ P 〈 0.01 ）. tl/2 of raltitrexed in blood plasma was （ 142.7 ± 39.1 ） h. Conclu- sion Raltitrexed can be quickly spread to relevant organs and tissues after intravenous injection, but it can not pass through the blood brain barrier easily. The metabolism of raltrexed in vivo is slow, and effective blood drug concentration can maintain for a long time.