氢溴酸右美沙芬咀嚼片的药代动力学和相对生物利用度

Pharmacokinetics and bioavailability of dextromethorphan chewable tablets

目的以氢溴酸右美沙芬片为对照药，氢溴酸右美沙芬咀嚼片为试验药进行人体生物利用度和药代动力学研究。方法１０名志愿者随机交叉口服单剂量６０ｍｇ氢溴酸右美沙芬片或咀嚼片，采用高效液相荧光法测定血浆中药物浓度。结果口服后药时曲线均符合一室模型。对照药和试验药的主要药代动力学参数如下，右美沙芬（ＤＭ）的药动学参数分别为Ｔ１／２：（２７５±０８７）ｈ，（２９２±１０３）ｈ；Ｔｍａｘ：（１８１±０５９）ｈ，（１７５±０６５）ｈ；Ｃｍａｘ：（３１０９±１１０１），（３３０９±１３４８）μｇ·Ｌ－１；ＡＵＣ：（１６９１２±８２９４），（１６６９５±７８２３）μｇ·ｈ－１·Ｌ－１；其相对生物利用度（Ｆ％）为（１０４０２±１０３７）。主要活性代谢物去甲右美沙芬（ＤＰ）的药动学参数分别为Ｔ１／２：（３０９±１０６）ｈ，（２９５±１０８）ｈ；Ｔｍａｘ：（２３０±０４８）ｈ，（１９０±０７０）ｈ；Ｃｍａｘ：（８３８５５±３２３７８），（８２８３７±３１９３５）μｇ·Ｌ－１；ＡＵＣ：（４１７７４３±１０７７７９），（４１４３１１±１２７３７６）μｇ·ｈ－１·Ｌ－１；相对?

AIM The pharmacokinetic profiles and the bioavailability of dextromethorphan chewable tablets were studied in 10 normal male volunteers METHODS Dextromethorphan was administered in a single dose of 60 mg in random order The plasma concentration of dextromethorphan and its main metabolite,dextrorphan,were determined by HPLC fluorescene method RESULTS The characteristics of the plasma concentration time curve fitted to one compartment model The pharmacokinetic parameters for dextromethorphan tablets and chewable tablets were as follows respectively:DM: T 1/2 :(2 75±0 87) h ,(2 92±1 03) h; T max :(1 81±0 59) h,(1 75±0 65) h; C max :(31 09±11 01),(33 09±13 48) μg·L -1 ;AUC:(169 12±82 94),(166 95±78 23) μg·h -1 ·L -1 ;the relative bioavailability was (104 02±10 37)%. DP: T 1/2 :(3 09±1 06) h, (2 95±1 08) h; T max :(2 30±0 48) h ,(1 9±0 7) h; C max :(838 55±323 78),(828 37±319 4) μg·L -1 ;AUC:(4177 43±1077 79),(4143 11±1273 76) μg·h -1 ·L -1 . CONCLUSION The relative bioavailability was 99 26%±16 31%. The results of analysis of variance,two one sided tests and (1-2α)90% showed that two formulations were bioequivalent.