不同粒径的阳离子阿奇霉素泡囊体内生物等效性研究  

Bioequivalence of positive ion azithromycin niosomes in different particle sizes

作　　者：钟萌[1] 孙全[1] 冯悦[2] 万胜利[1] 张景勍[1] 

机构地区：[1]重庆医科大学药物高校工程研究中心,重庆400016 [2]泸州医学院附属医院核医学科,四川泸州646000

出　　处：《第三军医大学学报》2014年第12期1295-1298,共4页Journal of Third Military Medical University

摘　　要：目的比较不同粒径的阳离子阿奇霉素囊泡及阿奇霉素(azithromycin,AM)原料药在大鼠体内的药代动力学参数,并计算其相对生物利用度。方法大鼠单剂量口服小粒径、大粒径阿奇霉素囊泡及阿奇霉素原料药后,采用HPLC法测定药物浓度,并用DAS2.1.1软件计算药代动力学参数并以统计矩参数Cmax、AUC0-t和tmax,通过双向单侧t检验和非参数检验判断3种制剂的生物等效性。结果小粒径阿奇霉素泡囊(AMNSS)和大粒径阿奇霉素泡囊(AMNSL)以及原料药AM体内的Cmax分别为18.73、9.2 mg/L和10.31 mg/L;tmax分别为6、4 h和2 h;AUC0-t分别为371.79、160.41 mg·h/L和136.09 mg·h/L;AUC0-∞分别为454.92、263.16 mg·h/L和158.50 mg·h/L;小粒径阿奇霉素泡囊和大粒径阿奇霉素泡囊相对生物利用度为273.19%、117.87%;经方差分析、双向单侧t检验和非参数检验,小粒径阿奇霉素泡囊和阿奇霉素、小粒径阿奇霉素泡囊和大粒径阿奇霉素泡囊体内有统计学差异(P<0.05)、而大粒径阿奇霉素泡囊和阿奇霉素体内无统计学差异(P>0.05)。结论小粒径阿奇霉素泡囊和阿奇霉素、小粒径阿奇霉素泡囊和大粒径阿奇霉素泡囊体内生物不等效,而大粒径阿奇霉素泡囊和阿奇霉素体内生物等效。Objective To compare the pharmacokinetic parameters and bioavailability of positive ion azithromycin niosomes and azithromycin solution in rats. Methods Drug concentrations in the plasma at different time points were determined by HPLC after single oral dose of small-particle-size azithromycin niosome （AMNSS）, large-particle-size azithromycin niosome （AMNSL） and azithromycin solution （AM） in rats. The pharmacokinetic parameters were calculated by DAS 2.1.1. Statistical moment parameters were adopted to calculate the pharmacokinetic parameters including Cmax, AUC0-t and tmax. Analysis of nonparametric tests and two one-sided t-tests were used to evaluate the bioequivalence of the 3 formulations.Results The pharmacokinetic parameters of AMNSS, AMNSL and AM in plasma were： Cmax 18.73, 9.2 and 10.31 mg/L, respectively; tmax 6, 4 and 2 h, respectively; AUC0-t 371.79, 160.41 and 136.09 mg·h/L, respectively; and AUC0-∞ 454.92, 263.16 and 158.50 mg·h/L, respectively. AMNSS and AMNSL relative bioavailability F0-t was 273.19% and 117.87%, respectively. The main pharmacokinetic parameters analyzed by variance, two side t-test and Wilcoxon rank sum test showed significant differences between AMNSS and AM, as well as AMNSS and AMNSL in vivo （P〈0.05）, but no significant difference between AMNSL and AM （P〉0.05）. Conclusion AMNSL and AM are bioequivalent, while AMNSS and AM are not, neither are AMNSS and AMNSL.

关 键 词：阿奇霉素 囊泡 粒径 生物等效性 

分 类 号：R944.9[医药卫生—药剂学] R969.1[医药卫生—药学]