糠酸莫米松鼻喷雾剂在中国健康成年受试者中的药代动力学研究

Pharmacokinetics study of mometasone furoate nasal spray in Chinese healthy adult subjects

目的评价糠酸莫米松鼻喷雾剂在中国健康受试者在空腹状态下的药代动力学特征和安全性。方法采用单剂量、随机、开放、空腹试验设计,入组36例中国健康成年受试者,受试者在空腹条件下经鼻腔吸入糠酸莫米松鼻喷雾剂200μg,用经验证的液相色谱串联质谱分析方法测定血浆中糠酸莫米松的浓度,用Phoenix WinNonlin(7.0)软件非房室模型分析方法对血浆中糠酸莫米松的药代动力学(PK)参数进行分析。记录给药后至随访结束的所有不良事件。结果糠酸莫米松主要血浆药代动力学参数:C_(max)、AUC_(0-t)、AUC_(0-∞)和t_(max)分别为(14.29±5.11)pg·mL^(-1)、(79.16±32.57)pg·mL^(-1)·h、(118.16±52.12)pg·mL^(-1)·h和0.94(0.50,1.50)h。不良事件发生率为30.56%。结论在空腹条件下,中国健康成年受试者糠酸莫米松鼻喷雾剂经鼻吸入后进入全身的血药浓度较低,安全性良好。

Objective To evaluate the pharmacokinetics and safety of mometasone furoate nasal spray in Chinese healthy subjects in fasting state.Methods A single dose,randomized,open,fasting experimental design was used.In this study,36 Chinese healthy adult subjects were enrolled and inhaled 200μg of mometasone furoate nasal spray through nasal cavity in fasting state.The concentration of mometasone furoate in plasma was determined by validated liquid chromatography by tandem mass spectrometry method.The non compartment model analysis method using Phoenix WinNonlin(7.0)software was used to analyze the pharmacokinetic(PK)parameters of mometasone furoate in plasma.Record all adverse events from administration to the end of follow-up.Results The main pharmacokinetics parameters of mometasone furoate:C_(max),AUC_(0-t),AUC_(0-∞)and t_(max)were(14.29±5.11)pg·mL^(-1),(79.16±32.57)pg·mL^(-1)·h,(118.16±52.12)pg·mL^(-1)·h and 0.94(0.50,1.50)h,respectively.The incidence of adverse events was 30.56%.Conclusion In fasting state,the blood concentration of mometasone furoate nasal spray entering the whole body after nasal inhalation is low,and the drug is safe.