摘要
目的：研究左旋多巴微囊漂浮片多剂量给药后在Beagle犬体内的生物等效性。方法：取犬6只,平均分为左旋多巴微囊漂浮片组和复方左旋多巴制剂组（多巴丝肼片,参比制剂）,每次ig 200 mg（以左旋多巴计）,每8 h给药1次,连续给药4 d,进行双周期交叉实验。以高效液相色谱法测定犬体内左旋多巴的血药浓度,计算药动学参数,评价生物等效性和左旋多巴稳态时的血药浓度波动情况。结果：左旋多巴微囊漂浮片和参比制剂在犬体内的cmax分别为（4.23±0.75）、（8.47±1.18）μg/ml,AUC（0-∞）分别为（12.18±1.16）、（13.81±2.12）μg·h/ml,tmax分别为（1.83±0.26）、（0.67±0.13）h;微囊漂浮片AUC（0-∞）与参比制剂AUC（0-∞）的几何均值比的90%置信区间为80.61%-97.90%,cmax几何均值比的90%置信区间为42.75%-57.63%;二者的tmax差异有统计学意义。二者血药浓度的波动度分别为（283.914±43.217）%、（506.489±78.965）%,波动系数分别为（177.463±7.873）%、（187.405±1.650）%,微囊漂浮片的波动度明显小于参比制剂。结论：左旋多巴微囊漂浮片具有良好的缓释特性;多剂量给药后与参比制剂吸收程度生物等效,且血药浓度的波动程度较小。
OBJECTIVE：To study the bioequivalence of Levodopa micro-capsule floating tablets in Beagle dogs after multidose administration.METHODS：6 dogs were collected and divided into Levodopa micro-capsule floating tablets group and Compound levodopa preparation group（Benserazide tablet,reference preparation）.They were given levodopa 200 mg intragastrically,every 8 h,for consecutive 4 day.In two-period crossover test,HPLC method was established to determine the concentration of levodopa in dog.The pharmacokinetic parameter,bioequivalence and plasma concentration fluctuation of steady state were calculated.RESULTS：The main pharmacokinetic parameters of Levodopa micro-capsule floating tablets and reference preparation were as that cmaxwere（4.23±0.75）and（8.47±1.18）μg/ml;AUC（0-∞）were（12.18±1.16）and（13.81±2.12）μg·h/ml;tmaxwere（1.83±0.26）and（0.67±0.13）h,respectively.90% confidence intervals for the geometric mean ratio of AUC（0-∞）for test and reference preparation were 80.61%-97.90%,and that for cmaxwere 42.75%-57.63%,respectively.There was statistical significance in tmaxbetween test and reference preparation.Degree of fluctuation of test and reference preparation at steady state were（283.914±43.217）% and（506.489±78.965）%,and fluctuation coefficient were（177.463±7.873）% and（187.405±1.650）%,respectively.The degree of fluctuation of test preparation was significantly less than that of reference preparation.CONCLUSIONS：Levodopa micro-capsule floating tablets show good sustained-release property,and are bioequivalent with reference preparation in absorption after multiple dose administration.It also has lesser fluctuation of blood concentration.
出处
《中国药房》
CAS
北大核心
2016年第16期2203-2206,共4页
China Pharmacy
基金
乌鲁木齐市科学技术计划项目(No.G121320003)
