左乙拉西坦对苯巴比妥血药浓度的影响

Impact of levetiracetam on plasma concentration of phenobarbital

目的:针对1例临床治疗中出现的左乙拉西坦(levetiracetam,LEV)剂量调整显著影响苯巴比妥(phenobarbital,PB)血药浓度的案例,初步探究其两药相互作用的机制。方法:(1)Wistar大鼠随机分为苯巴比妥单用组(60 mg·kg-1)与苯巴比妥+左乙拉西坦合用组(PB60 mg·kg-1+LEV150 mg·kg-1),单次给药后,检测苯巴比妥血药浓度。(2)Wistar大鼠随机分为常规剂量组(PB120 mg·kg-1·d-1+LEV300 mg·kg-1·d-1)与高剂量组(PB120 mg·kg-1·d-1+LEV600 mg·kg-1·d-1),分别给药27 d,于每日首次给药前眼眶采血监测苯巴比妥血药浓度,并于第27天给药后0.5 h,2 h,4 h眼眶采血并处死大鼠,检测苯巴比妥血药浓度和肝脏,肾脏,脑组织药物浓度。结果:(1)单用组(PB)与合用组(PB+LEV)相比较,单次给药后苯巴比妥在大鼠体内各时间点血药浓度无统计学差异(P>0.05)。(2)长期给药期间(共计27 d),高剂量组与常规剂量组相比,苯巴比妥血药浓度未见统计学差异(P>0.05)。(3)第27天给药后高剂量组与常规剂量组相比,苯巴比妥在0.5,2,4 h的血药浓度及脑组织,肝脏,肾脏药物浓度均无统计学差异(P>0.05)。结论:本实验显示常规剂量和高剂量的左乙拉西坦均不会改变大鼠体内苯巴比妥的血药浓度,且高剂量左乙拉西坦并未导致苯巴比妥脑药浓度,肝肾组织药物浓度发生显著性变化。

OBJECTIVE To investigate the mechanism of interaction between levetiracetam（LEV） and phenobarbital（Pl3） ;according to a clinical case, it might be induced by levetiracetam （LEV） that the serum concentration of phenobarbital （PB） decreased.. METHODS （1） Wistar rats were received PB（60 mg· kg-1 ）iv alone or in combination with LEV per os （150 mg· kg-1 ）, respectively. The blood samples withdrawn at different time points were determined by HPLC. （2） The rats were divid- ed in to two groups： the routine-dose group（PB 120 mg· kg-1·d-1 ＋ LEV 300 mg^kg ~ ~d-1 ）and the high-dose group（PB 120mg· kg-1·d-1 ＋ LEV 600 mg· kg-1·d-1）. The rats were administered for 27 days and the blood samples were collected from the periorbital plexus everyday. The rats were sacrificed after administration of LEV and PB on 27th day. Blood samples and tissue samples were collected at 30, 120, 240 min after the last time of administration and were determined by HPLC. RE- SULTS （1） There was no significant difference in plasma concentration of PB between the single group and the combined group at different time points in rats （P〈0. 05）. （2） The concentration of PB in the routine-dose group was not different from the high-dose group （P〈0. 05）. （3） There was no difference of concentration of PB in blood, liver, kidney and brain between the high-dose group and the routine-dose group at 30, 120, 240 min after administration of PB and LEV on 27th day （P〈 0. 05）. CONCLUSION Routine dose and high dose of LEV could not affect the blood concentration of PB in rats and high dose of LEV could not impact on the concentration of PB in kidney, liver and brain.