复方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研究
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篇名: 复方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研究
TITLE:
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,AUC0-∞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AUC0-∞与参比制剂AUC0-∞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。
ABSTRACT: OBJECTIVE: To study the bioequivalence of Levodopa micro-capsule floating tablets in Beagle dogs after multi- dose 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 cmax were (4.23±0.75) and (8.47±1.18) μg/ml; AUC0-∞ were (12.18±1.16) and (13.81±2.12) μg·h/ml; tmax were(1.83±0.26) and (0.67±0.13) h, respectively. 90% confidence intervals for the geometric mean ratio of AUC0-∞ for test and reference preparation were 80.61%-97.90%, and that for cmax were 42.75%-57.63%, respectively. There was statistical significance in tmax between 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.
期刊: 2016年第27卷第16期
作者: 陈雪珊,滕亮,贺鑫韬,马桂芝
AUTHORS: CHEN Xueshan,TENG Liang,HE Xintao,MA Guizhi
关键字: 左旋多巴;微囊;漂浮片;复方左旋多巴制剂;高效液相色谱法;生物等效性;波动程度
KEYWORDS: Levodopa; Micro-capsule; Floating tablets; Compound levodopa preparation; HPLC; Bioequivalence; Fluctuation degree
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