阿奇霉素分散片人体药动学和相对生物利用度研究

Pharmacokinetcs and bioequivalence of azithromycin dispersible tablets in healthy volunteers

目的对阿奇霉素血药浓度测定方法进行改进,研究阿奇霉素分散片的相对生物利用度。方法20名男性健康受试者随机交叉双周期给药,分别口服单剂量阿奇霉素试验制剂及参比制剂500 mg后于不同的时间点采血,100μL血样经乙腈沉淀蛋白后,HPLC-MS/MS检测。DAS2.0软件计算两者的药物动力学参数,并评价试验制剂的生物等效性。结果阿奇霉素在1~1 000 ng.mL-1范围内线性好,日内或日间差均小于1 0%,准确度在97%~110%。稳定性良好。萃取回收率至少大于91%。受试药与对照药的药动学参数t1/2,Tmax,Cmax,AUC0~t,AUC0~∞,分别为：（40.3±6.5）h,（2.1±0.7）h,（541.7±179.4）ng.mL-1,（4 772.4±913.9）ng.h.mL-1,（5 346.9±1 300.0）ng.h.mL-1和（35.6±5.1）h,（1.8±0.5）h,（584.9±147.3）ng.mL-1,（5 059.5±1347.4）ng.h.mL-1,（5 480.5±1 484.3）ng.h.mL-1。结果显示：单剂量给药后,阿奇霉素受试制剂的相对生物利用度为（99.4%±28.3%）。结论本方法简单快速,灵敏可靠,成功应用于阿奇霉素生物等效性研究,阿奇霉素试验制剂相对参比制剂生物等效。

Objective To improve the determination of azithromycin in human plasma, and study the relative bioavailability of azithromycin dispersible tablets. Methods A single oral dose of 500 mg test and reference formulations was given to 20 healthy volunteers in a randomized cross-over study. Sample （0. 1 mL） was determined by HPLC-MS/MS after proteinum precipitation by acetonitril. DAS 2. 0 was used to assess pharmacokinetcs bioavailability and bioequiv- alence of azithromycin dispersible tablets. Results The linear range of the calibration curves was 1-1000 ng · mL -1 for azithromycin with a lower limit of quantitation （ 1ng ·mL-1 ）. Within- and between-run precision was less than 10%. Accuracy ranged 97 % - 110%. The recovery was above 91%. The main pharmacokinetic parameters t1/2, tmax, Cmax, AUC0-t, AUC0-∞were （40.3±6.5） h, （2.1±0.7） h, （541.7±179.4） ng·mL-1, （4 772.4±913.9）ng ·h ,mL-1, （5 346.9±1 300.0） ng·h ·mL-1 and （35.6±5.1） h, （1.8±0.5） h, （584. 9±147.3） ng·mL-1, （5 059.5±1 347.4） ng · h· mL-1, （5 480. 5±1 484. 3） mg· h · mL-1, respectively. The relative bioavailability of azithromycin test reference was （99. 4%±28. 3%）. Conclusion The present method is sensitive, effiective, and reliable. The method described has been successfully used for bioequivalence study of an azithromycin formulation product. The test and reference azithromycin dispersible tablets are bioequivalent.