双成分测定评价盐酸甲氯芬酯胶囊的人体生物等效性  

Bioequivalence study of Meclofenoxate hydrochloride capsules by determination of dualactive metabolites

作　　者：南峰 唐诗韵[1] 叶薇 陈朝霞 丁红[1] 阎博华[1] 曾洁萍[1] NAN Feng;TANG Shiyun;YE Wei;CHEN Zhaoxia;DING Hong;YAN Bohua;ZENG Jieping(GCP Centre,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan,610072 P.R.China)

机构地区：[1]成都中医药大学附属医院GCP中心,四川成都610072

出　　处：《华西药学杂志》2021年第4期415-418,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:081973911)。

摘　　要：目的通过研究两种活性代谢成分的体内药动学来评价盐酸甲氯芬酯胶囊制剂的人体生物等效性。方法采用交叉试验设计,21位健康受试者单次口服300 mg盐酸甲氯芬酯后,分别用HPLC法和LC-MS法检测对氯苯氧乙酸(4-CPA)和二甲氨基乙醇(DMAE)的经时血浆浓度,用WinNonlin软件计算药动学参数并评价两个制剂的生物等效性。结果4-CPA的C_(max)分别为27.36±4.18、26.16±4.27 mg·L^(-1),AUC_(0-t)分别为230.27±68.05、211.08±62.57 h·mg·L^(-1),AUC_(0-∞)分别为238.89±71.68、218.96±65.80 h·mg·L^(-1)。DMAE的C_(max)分别为277.66±107.25、266.18±118.37μg·L^(-1),AUC_(0-t)分别为721.05±172.72、736.03±216.90 h·μg·L^(-1),AUC_(0-∞)分别为776.17±203.89、835.52±269.99 h·μg·L^(-1)。两种制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)的90%置信区间均在等效范围(80.0%~125.0%)内。结论两种制剂生物等效,4-CPA和DMAE的体内分布和代谢存在显著差异。OBJECTIVE To evaluate the bioequivalence of two Meclofenoxate hydrochloride capsules by studying the pharmacokinetics of two active metabolites.METHODS 21 healthy subjects received single dose of two capsule preparations under a cross-over design.After orally taken 300 mg Meclofenoxate hydrochloride,the plasma concentration of 4-CPA and DMAE were measured by HPLC and LC-MS method,respectively.The data were calculated by WinNonlin software to evaluate the bioequivalence.RESULTS The main pharmacokinetic parameters of test capsule and reference capsule were as follows:for 4-CPA,the C_(max) was 27.36±4.18 mg·L^(-1)and 26.16±4.27 mg·L^(-1);AUC_(0-t) was 230.27±68.05 h·mg·L^(-1)and 211.08±62.57 h·mg·L^(-1);AUC_(0-∞)was 238.89±71.68 h·mg·L^(-1)and 218.96±65.80 h·mg·L^(-1).For DMAE,the C_(max) was 277.66±107.25μg·L^(-1)and 266.18±118.37μg·L^(-1);AUC_(0-t)was 721.05±172.72 h·μg·L^(-1)and 736.03±216.90 h·μg·L^(-1);AUC_(0-∞)was 776.17±203.89 h·μg·L^(-1)and 835.52±269.99 h·μg·L^(-1).The 90%CI of C_(max),AUC_(0-t) and AUC_(0-∞)all fell within the equivalent range(80.0%^(-1)25.0%).CONCLUSION The two capsule preparations are bioequivalent.There are significant differences in the distribution and metabolism of 4-CPA and DMAE.

关 键 词：氯酯醒 盐酸甲氯芬酯 对氯苯氧乙酸 二甲氨基乙醇 代谢物 血药浓度 药动学 生物等效性 

分 类 号：R917[医药卫生—药物分析学]