【摘要】 目的探讨在Beagle犬体内,培美曲赛二钠和奥沙利铂联合用药前后药动学变化规律。方法采用自身对照随机交叉法,将9只Beagle犬随机分成培美曲赛二钠组、奥沙利铂组以及培美曲赛二钠和奥沙利铂联合给药组,经静脉给药后,于不同时间点采集血样,LC-MS/MS法测定二者的血药浓度,DAS3.2.1统计矩法计算药动学参数,AUC和Cmax用"生物等效性与生物利用度"模块下的90%可信区间法进行统计。结果与单独给药比较,联合使用培美曲赛二钠和奥沙利铂的主要药动学参数t1/2、CLint和MRT均无显著性差异(P>0.05);药物单用与合用组的AUC和Cmax在90%可信区间的生物等效性统计结果合格,tmax检验结果差异无统计学意义(P>0.05)。结论 Beagle犬同时注射培美曲赛二钠和奥沙利铂不存在显著的药动学相互作用。更多还原

【Abstract】 Objective The purpose of this study is to investigate the pharmacokinetic interaction of pemetrexed disodium and oxaliplatin in healthy adult Beagle dogs following single and multiple oral dose administration.Methods Nine Beagle dogs were divided into pemetrexed disodium group,oxaliplatin group,pemetrexed disodium and oxaliplatin group.Blood samples were collected at intervals after each intervenous administration.Then the plasma concentration was determined by LC-MS/MS,and the pharmacokinetic parameters were calculated by DAS3.2.1 statistical moment method.AUC and Cmax was calculated by using 90% confidence interval method of bioequivalence and bioavailability.Results Compared with the separate administration,the main pharmacokinetic parameters(t1/2,CLintand MRT)had no significant difference(P>0.05);The 90% confidence intervals for bioequivalence statistics of drugs alone and in combination group were qualified,and tmaxtest showed no significant difference(P>0.05).Conclusion Pemetrexed disodium and oxaliplatin have no pharmacokinetic interaction in Beagle dogs.更多还原