利培酮与阿立哌唑在大鼠体内药物-药物相互作用研究

Drug-Drug Interaction Studies of Risperidone and Aripiprazole in Rats

本文旨在探究利培酮(RIS)与阿立哌唑(ARI)联合用药时发生药物-药物相互作用(DDI)的可能性.实验分别考察利培酮或阿立哌唑单独给药和利培酮与阿立哌唑联合给药后利培酮与阿立哌唑在大鼠体内药代动力学行为,通过液相色谱串联质谱方法(LC-MS/MS)同时测定大鼠体内利培酮和阿立哌唑及两者活性代谢产物9-羟基利培酮(9-OH-RIS)、脱氢阿立哌唑(DE-ARI)的浓度,通过Winnonlin软件非房室模型计算药动学参数.实验结果表明:利培酮、9-羟基利培酮的暴露量分别为单独用药组的1.70倍、1.75倍(P<0.05),而利培酮对阿立哌唑没有显著影响.阿立哌唑显著增加了利培酮及其代谢产物9-羟基利培酮在大鼠体内的暴露量,提示两者临床在合并用药时需关注利培酮及其代谢物的血药浓度.

The possibility of drug-drug interaction(DDI)is investigated when risperidone is combined with aripiprazole.The pharmacokinetic behavior of risperidone and aripiprazole in rats is observed after using risperidone or aripiprazole alone and combined.Risperidone,aripiprazole,and their active metabolites 9-hydroxyrisperidone and dehydroaripiprazole,are determined by mass spectrometry(LC-MS/MS),and the pharmacokinetic parameters are calculated by Winnonlin software with non-compartmental model.The results show that the exposures of risperidone and 9-hydroxyrisperidone after risperidone combined with aripiprazole are 1.70 times and 1.75 times(P<0.05)higher than alone group,respectively.While risperidone had no significant effect on aripiprazole.It is concluded that aripiprazole significantly increases the exposure of risperidone and the metabolite 9-hydroxyrisperidone in rats,suggesting that the plasma concentration of risperidone and its metabolites should be considered when the two drugs are combined.