癫痫患者丙戊酸与拉莫三嗪药代动力学相互作用研究

目的 考察癫痫患者合用丙戊酸(VPA)与拉莫三嗪(LTG)的药代动力学相互作用.方法 将纳入的癫痫患者随机分为3组:VPA组276例、LTG组254例和合用组334例.VPA组患者每天口服VPA 500～1000 mg,LTG组每天口服LTG 100～200 mg,合用组用VPA+LTG.高效液相色谱-质谱联用法测定V...

Pharmacokinetic interaction between valproic acid and lamotrigine in Chinese patients with epilepsy

Objective To investigate the pharmacokinetic interaction between valproic acid(VPA)and lamotrigine(LTG)in epileptic patients.Methods The epilepsy patients were randomly divided into three groups:VPA group(276 cases),LTG group(254 cases)and VPA combined with LTG group(334 cases).Patients in the VPA group and LTG group were given oral administration VPA of 500-1000 mg·d^-1 and LTG of 100-200 mg·d^-1.VPA combined with LTG group were VPA+LTG.The morning trough plasma concentrations of VPA and its major metabolites and LTG were determined by HPLC-MS/MS method to analyze the change of serum concentration of two drugs used alone or in combination.Results The median,25%,and 75%quartiles of LTG concentration to weight adjusted dose ratio(CDR)in combination therapy with VPA group were significantly higher than that of LTG group(3.26[2.51-4.10](μg·mL^-1)·(mg·kg^-1)-1 vs 1.23[0.90-1.60](μg·mL^-1)·(mg·kg^-1)-1,P<0.0001).The CDR of 3-keto-VPA,3-OH-VPA,4-OH-VPA,4-ene-VPA and 5-OH-VPA were significantly higher than those of VPA group(P<0.0001).However,there was no significant difference in plasma concentrations of VPA prototype and its metabolite 2-ene-VPA.Conclusion The combination of VPA with LTG can significantly increase LTG,CDR with a dose-related relationship,and combining LTG can significantly increase the CDR of VPA major metabolites.