卡马西平对丙戊酸稳态血药浓度及药物动力学的影响  

Effect of Carbamazepine on Pharmacokinetics of Valproic acid at Steady State

作　　者：孙成春[1] 俞学忠[2] 张黎明[1] 

机构地区：[1]中国人民解放军济南军区总医院药理科,山东济南250031 [2]第二军医大学

出　　处：《解放军药学学报》2003年第5期355-357,共3页Pharmaceutical Journal of Chinese People's Liberation Army

摘　　要：目的　观察兔灌服卡马西平前后对稳态时丙戊酸血药浓度及药代动力学参数的影响。方法　实验分为两期 ,Ⅰ期 :7只兔单独灌服丙戊酸 ,连续给药 4d至稳态后定时采血 ;Ⅱ期 :合用卡马西平与丙戊酸 7d。给药剂量丙戊酸为 30mg·kg-1 ·d-1 ,卡马西平为 4 0mg·kg-1 ·d-1 。采用荧光偏振免疫分析法测定丙戊酸血药浓度。对两期药代动力学参数进行统计分析。结果　合并用药后 (Ⅱ期 )峰值时间内VPA血药浓度 (0 .5 ,1 .0h)比单独应用VPA(Ⅰ期 )的浓度显著升高 ,二者有显著性差异 (P <0 .0 1 ,P <0 .0 5 )。其余时间点的血药浓度值尽管有变化 ,但无统计学意义。合并用药后VPA的消除半衰期 (T1 / 2 β　 )低于单用者 ,二者有显著性差异 (P <0 .0 5 )。合并用药后血浓度达峰时间提前 ,但与单用药比较差异无统计学意义 ,其它药动学参数无显著性差异。结论　CBZ可以使VPA的峰浓度显著升高 ,而使其T1 / 2　缩短 ,二药合用时应注意监测VPA的血药浓度 ,及时调整给药剂量。Aim To observe the effects of oral Carbamazpine(CBZ) on serum concentrations at steady state and its pharmacokinetics of Valproic acid(VPA) in New Zealand rabbits.Methods The experiment was divided into 2 stages.(Ⅰ)The rabbits only received a four-day course of oral VPA until steady state.(Ⅱ)VPA combined with CBZ seven days.The dose of VPA is 30mg·kg -1 ·d -1 and the dose of CBZ is 40mg·kg -1 ·d -1 for rabbits.The serum concentration of VPA was determined by FPIA.The two series of pharmacokinetics parameters were analysed by statistic method.Results There was significant increasing of VPA blood concentration at peak value time(0.5 and 1.0h) in Ⅱ stage (P<0.01,P<0.05).The VPA blood concentration hadn't statistic meaning at the others time though they had change.The eliminate(T 1/2β )of VPA in Ⅱ stage was notable lower than that of Ⅰstage.The other pharmacokinetics parameters were not changed significantly between two stages.Conclusion The Cmax of VPA was notabale increased and its T 1/2 was shortened in Ⅱ stage.It is necessary monitored the blood concentration of VPA and changed the therapeutic dose of VPA when it is taken with CBZ.

关 键 词：卡马西平 丙戊酸 血药浓度 药物代谢动力学 抗癫痫药 

分 类 号：R971.6[医药卫生—药品] R969.1[医药卫生—药学]