摘要
目的：研究美敏伪麻缓释胶囊经单、多次给药后的药动学特征，评估其在健康志愿者体内的安全性。方法22例受试者随机、开放试验设计，研究单、多次给药药动学特征。血浆中氯苯那敏、伪麻黄碱、右美沙芬、右啡烷采用LC-MS/MS法测定，药动学参数采用WinNonlin软件计算。安全性特征以记录到的所有不良事件来进行评价。结果整个研究过程中没有严重不良事件报告。单次口服美敏伪麻缓释胶囊后，伪麻黄碱、氯苯那敏、右美沙芬和右啡烷均在3～5 h达峰，t1/2分别为6.30±1.17、23.3±6.91、10.4±2.19、8.62±3.04 h，Cmax分别为203±40.4、5.05±1.39、4.29±3.95、1.95±0.72 ng/mL， AUClast分别为2050±559、137±47.5、61.3±67.5、17.2±6.58μg＆#183;h/L，AUCinf分别为2140±570、161±63.8、17.6±6.65、62.8±69.3μg＆#183;h/L。在2次/d，连续给药4 d后基本达到稳态血药浓度，伪麻黄碱、氯苯那敏、右美沙芬和右啡烷的Cmax、Cmin、AUCtau, ss与单次给药比较均有不同程度的升高，波动系数的平均值为107%～271%。结论美敏伪麻缓释胶囊多次给药后4 d达到稳态血药浓度，暴露均较单次给药后有所增高，在健康志愿者体内安全性良好。
Objective To investigate pharmacokinetics of Dextromethorphan Chlorpheniramine Pseudoephedrine Controlled-release Capsule after single and multiple doses, and make an assessment on the security in healthy volunteers.Methods Random and open trial was carried out for 22 healthy volunteers. A single and multiple oral dose of Dextromethorphan Chlorpheniramine Pseudoephedrine Controlled-release Capsule were given. The concentrations of dextromethorphan, chlorpheniramine, pseudoephedrine, and dextrorphan in plasma were determined by LC-MS/MS method. Pharmacokinetic parameters were calculated using WinNonlin program. Safety was evaluated using observed adverse events.Results No observed severe adverse event was reported. For chlorpheniramine, pseudoephedrine, dextromethorphan, and dextrorphan, median oftmax were about 3.0 — 5.0 h,means of t1/2 were 6.30 ± 1.17, 23.3 ± 6.90, 10.4 ± 2.19, and 8.62 ± 3.04 h. Means ofCmax were 203 ± 40.4, 5.05 ± 1.39, 4.29 ± 3.95, and 1.9 5 ± 0.720 ng/mL. Means of AUClast were 2 055 ± 559, 137 ± 47.5, 61.3 ± 67.5, and 17.2 ± 6.58. Means of AUCinf were 2 140 ± 570, 161 ± 63.8, 17.6 ± 6.65, and 62.8 ± 69.3μg＆#183;h/L after single dose. After four-day continuous dosing, steady status was reached for all compounds. TheirCmax,Cmin, and AUCtau, ss increased by different extent, and FI were within the range of 107% — 271%.Conclusion Dextromethorphan Chlorpheniramine Pseudoephedrine Controlled-release Capsule reaches steady status after four-day continuous doses, plasma exposures of four compounds increase than those after single dose, and capsule are well tolerated in healthy volunteers.
出处
《现代药物与临床》
CAS
2015年第6期622-628,共7页
Drugs & Clinic
基金
国家自然科学基金资助项目(81403013)
国家科技重大专项(2012ZX09303006-002)
北京协和医院中青年基金资助项目(pumch-2013-118)
关键词
美敏伪麻缓释胶囊
氯苯那敏
伪麻黄碱
右美沙芬
右啡烷
药动学
LC-MS/MS
Dextromethorphan Chlorpheniramine Pseudoephedrine Controlled-release Capsule
chlorpheniramine
pseudoephedrine
dextromethorphan
pharmacokinetics
LC-MS/MS
