复方愈麻美芬缓释片在健康志愿者体内药动学研究

Pharmacokinetics of Compound Yumameifen Sustained-release Tablets in healthy volunteers

目的研究复方愈麻美芬缓释片单剂量和多剂量给药在健康志愿者体内的药动学规律。方法采用自身对照的双周期交叉试验设计,12名健康受试者单次和多次口服受试制剂复方愈麻美芬缓释片或相应的参比制剂,不同时间点收集血样,采用LC/MS/MS法测定血浆中愈创甘油醚、伪麻黄碱、右美沙芬和O-去甲右美沙芬的浓度。药动学参数采用DAS软件处理获得。结果单剂量口服受试制剂后,愈创甘油醚、伪麻黄碱、右美沙芬、O-去甲右美沙芬的主要参数为tmax:1.09±0.42、3.68±1.62、5.05±2.29、3.82±1.25 h;t1/2:3.32±3.54、6.20±0.97、12.2±3.1、7.60±0.97 h;Cmax:499±159、96.1±12.9、1.82±1.18、142±34 ng/m L;AUC0-t:2 363±529、1 359±284、31.4±23.6、1 504±242 ng·h/m L;AUC0-∞:2 554±639、1 395±303、38.4±28.4、1 563±248 ng·h/m L。多剂量口服愈创甘油醚、伪麻黄碱、右美沙芬、O-去甲右美沙芬的主要参数为Cmax:709±298、169±27、9.64±6.36、314±96 ng/m L;Cmin:48.9±25.4、50.8±13.9、5.45±5.53、110±45 ng/m L;tmax:8.27±5.71、7.64±4.99、8.27±6.57、7.55±5.99 h;AUC0-t:5 277±2 212、2 741±508、199±198、4 964±1 387 ng·h/m L;AUC0-∞:5 718±2 176、2 750±511、220±226、5 196±1 506 ng·h/m L。结论复方愈麻美芬缓释片各成分药动学具有明显的缓释特征。

Objective To evaluate the pharmacokinetics of Compound Yumameifen Sustained-release Tablets in healthy volunteer. Methods In a randomized crossover trial, 12 healthy subjects received a single oral dose or multiple oral doses of either test tablets Compound Yumameifen Sustained-release Tablets or reference tablet. The concentrations of guaifenesin, pseudoephedrin, dextromethorphan, and O-dextrorphan in plasma were determined by LC/MS/MS method. Pharmacokinetic parameters were obtained using DAS program. Results After single oral administration of test tablets, the mean pharmacokinetic parameters of guaifenesin, pseudoephedrin, dextromethorphan, and O-dextrorphan were as follows： tmax were 1.09 ± 0.42, 3.68 ± 1.62, 5.05 ± 2.29, 3.82 ± 1.25 h; t1/2 were 3.32 ± 3.54, 6.20 ± 0.97, 12.2 ± 3.1, 7.60 ± 0.97 h; Cmax were 499 ± 159, 96.1 ± 12.9, 1.82 ± 1.18, 142 ± 34 ng/m L; AUC0-t： 2 363 ± 529, 1 359 ± 284, 31.4 ± 23.6, 1 504 ± 242 ng·h/m L; AUC0-∞ were 2 554 ± 639, 1 395 ± 303, 38.4 ± 28.4, 1 563 ± 248 ng·h/m L. After multiple oral administration of test tablets, the mean pharmacokinetic parameters of guaifenesin, pseudoephedrin, dextromethorphan, and O-dextrorphan were as follows： Cmax were 709 ± 298, 169 ± 27, 9.64 ± 6.36, 314 ± 96 ng/m L; Cmin were 48.9 ± 25.4, 50.8 ± 13.9, 5.45 ± 5.53, 110 ± 45 ng/m L; tmax were 8.27 ± 5.71, 7.64 ± 4.99, 8.27 ± 6.57, 7.55 ± 5.99 h; AUC0-t were 5 277 ± 2 212, 2 741 ± 508, 199 ± 198, 4 964 ± 1 387 ng·h/m L; AUC0-∞ were 5 718 ± 2 176, 2 750 ± 511, 220 ± 226, 5 196 ± 1 506 ng·h/m L. Conclusion The components in Compound Yumameifen Sustained-release Tablets have the characteristic of slow releasing properties.