L-苏糖酸阿奇霉素大鼠体内药代动力学研究

Pharmacokinetics of Azithromycin L-threonate in Rats

目的观察L-苏糖酸阿奇霉素在大鼠体内药代动力学特征。方法建立L-苏糖酸阿奇霉素液-质联用检测分析方法,测定L-苏糖酸阿奇霉素灌胃给药后不同时间点大鼠血浆L-苏糖酸阿奇霉素的浓度。采用DAS2.0软件计算其主要药代动力学参数并和乳糖酸阿奇霉素进行比较。结果大鼠灌胃给予L-苏糖酸阿奇霉素(60mg·kg-1)和等摩尔乳糖酸阿奇霉素的主要药代动力学参数:AUC(0-t)分别为(366.14±241.15)mg·L-1·h-1和(321.79±118.71)mg·L-1·h-1,Cmax分别为(50.04±13.46)mg·L-1和(51.08±16.24)mg·L-1,Tmax分别为(1.08±0.20)h和(1.17±0.26)h,MRT(0-t)分别为(7.88±3.93)h和(7.75±3.21)h,t1/2z分别为(42.93±8.95)h和(47.75±24.19)h,CLz分别为(0.121±0.05)L·h-1·kg-1和(0.126±0.053)L·h-1·kg-1,Vz分别为(7.25±2.25)L·kg-1和(7.75±2.58)L·kg-1。经t检验,两药间上述主要药代动力学参数比较差异无统计学意义(P>0.05)。结论 L-苏糖酸阿奇霉素和乳糖酸阿奇霉素灌胃给药在大鼠体内药代动力学过程相似。

Objective To study the pharmacokinetic feature of azithromycin L-threonate in rats. Methods The plasma concentrations of azithromycin L-threonate were determined by LC- MS at different time points after intragastric administration. The pharmacokinetic parameters were calculated by DAS 2.0 software and were compared with azithromycin lactobionate. Results After intragastric administration, AUC （0-t）, Cmax, Tmax, MRT （0-t）, tl/2z, CLz and Vz were, respectively, （366.14±241.15 ）rag- L^-1 · h^-l, （50.04±13.46）mg· L^-1, （1.08±0.20）h, （7.88±3.93）h,（42.93±8.95）h,（0.121±0.05）L·h^-1· kg^-1 and （7.25±2.25）L· kg^-l for azithromycinL-threonate,-and （321.79±118.71）mg· L ^-1·h^-1,（ 51.08±16.24）mg· L^-1, （1.17±0. 26 ）h,（7. 75±3. 21 ）h,（ 47. 75±24. 19） h,（0. 126±0.053） L·h^-1·kg^-1 and （7.75±2.58） L · kg^-1 for azithromycin lactobionate. There were no significant differences in these parameters between azithromycin L-threonate and azithromyein lactobionate （P 〉 0. 05）. Conclusion Azithromycin L-threonate and azithromycin lactobionate have similar pharmacokinet〈 ics in rats.