罗红霉素与氨溴索药动学相互作用研究

Study on Pharmacokinetic Interaction Between Roxithromycin and Ambroxol in Human

目的研究复方罗红霉素氨溴索片中两药在体内是否存在药动学上相互作用。方法24名健康男性志愿者,采用4×4交叉试验设计,每组1人,交叉服用复方罗红霉素氨溴索片、罗红霉素片加氨溴索片、罗红霉素片、氨溴索片,服药后不同时间点取肘静脉血4～5mL,血药浓度采用HPLC/MS测定。计算药动学参数,并进行方差分析,以90%的可信区间进行药物发生相互作用是否具临床意义的判定。结果复方制剂、合用药物以及单用药物药动学参数均无显著性差异。无论是复方或是合用2种药物,均未产生有临床意义的药动学相互作用。结论罗红霉素氨溴索片中2种成分在体内不产生统计学上和临床意义的药动学相互作用。

OBJECTIVE To evaluate pharmacokinetic interaction of oral administrated roxithromycin-ambroxol tablets （complex prescription）. METHODS The study was conducted in a self-controlled,four-period cross-over experiment in 24 healthy volunteers. The volunteers received complex prescription roxithromycin-ambroxol tablets（roxithromycin 300 mg,ambroxol 60 mg）,or co-administration roxithromycin tablets（300 mg） and ambroxol tablets（60 mg）,or roxithromycin tablets （300 mg） ,or ambroxol tablets（60 mg） for 7 consecutive days. On the 7th day,serial blood samples were drawn before and at 0.5,1,1.5,2,3,4,6,8,12,24,36,48,72 h after drug administration. The concentrations of roxithromycin and ambroxol in plasma were measured by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry （HPLC-ESI-MS）. Non-compartmental analysis was used to characterize roxithromycin or ambroxol plasma concentration-time profiles,and comparisons of mean values were analyzed by the analysis of variance. Differences were considered to be significant at P0.05. Drug-drug interaction was tested by 90% confidence interval. RESULTS The pharmacokinetic parameters of roxithromycin or ambroxol were not changed in volunteers treated with 4 difference medicine. CONCLUSION Roxithromycin and ambroxol do not produce pharmacokinetic interaction in human.