氨酚伪麻美芬片Ⅱ在健康人体内的药动学和生物等效性

目的研究2种国产氨酚伪麻美芬片Ⅱ在健康人体内的药动学及生物等效性。方法20名健康男性受试者按2制剂双周期交叉试验设计口服受试制剂和参比制剂各2片,采用高效液相色谱-紫外法测定血浆中对乙酰氨基酚的浓度,高效液相色谱-质谱联用法测定血浆中伪麻黄碱和右啡烷的浓度,使用DAS软件计算药动学参数并进行生物等效性统计分析。结果参比制剂和受试制剂中对乙酰氨基酚的c_(max)分别为(6 600±s 1200),(7600±2100)μg·L~(-1);t_(max)分别为(1.1±0.6),(0.9±0.6)h;A4 UC_(0～16)分别为(27 900±4700),(28 700±4 400)μg·h·L~(-1);t(1/2)分别为(4.0±1.0),(4.2±1.4)h;伪麻黄碱的C_(max)分别为(213±33),(222±34)μg·L~(-1);t_(max)分别为(1.8±0.5),(1.6±0.6)h;AUC_(0～24)分别为(1 676±261),(1 659±282)μg·h·L~(-1);t_(1/2)分别为(4.6±0.5),(4.6±0.5)h;右啡烷的c_(max)分别为(7±4),(7.5±2.9)μg·L~(-1);t_(max)分别为(2.1±0.6),(1.9±0.7)h;AUC_(0～24)分别为(38±15),(39±12)μg·h·L~(-1);t_(1/2)分别为(6±3),(5.1±2.7)h。以AUC_(0～t)计算,受试制剂中对乙酰氡基酚、伪麻黄碱和右美沙芬的相对生物利用度分别为(103±8)%,(100±18)%,(109±27)%,2种制剂的主要药动学参数经统计学检验,差异无显著意义(P>0.05)。结论2种制剂具有生物等效性。

Pharmacokinetic and bioequivalence of paracetamol,pseudoephedrine and dextromethorphan tablets Ⅱ in healthy volunteers

AIM To study the pharmacokinetics and bioequivalence of two kinds of domestic paracetamol, pseudoephedrine and dextromethorphan tabletsⅡin healthy human subjects.METHODS In a randomized crossover study,20 healthy male volunteers were given a single oral dose of the two preparations(containing 650 mg of paracetamol,60 nag of pseudoephedrine,30 mg of dextrornethorphan)including test preparation and reference preparation.The concentration of paracetamol in plasma was determined by HPLC.The concentrations of pseudoephedrine and dextrorphan in plasma were determined by LC-MS/MS(ESI).The pharmacokinetic parameters were processed by DAS program for statistic analysis.RESULTS The pharmacokinetic parameters of the reference and test preparations for paracetamol were as follows:c_(max)(6600±s 1200)vs(7600±2100)μg·L~(-1);t_(max)(1.1±0.6)vs(0.9±0.6)h;AUC_(0-16)(27900±4700)vs(28700±4400)μg·h·L~(-1); t_(1/2)(4.0±1.0)vs(4.2±1.4)h,respectively.The pharmacokinetic parameters of the reference and test preparations for pseudoephedrine were as follows:c_(max)(213±33)vs(222±34)μg·L~(-1);t_(max)(1.8±0.5)vs (1.6±0.6)h;AUC_(0-24)(1676±261)vs(1659±282)μg·h.L~(-1)t_(1/2)(4.6±0.5)vs(4.6±0.5)h, respectively.The pharmaeokinetic parameters of the reference and test preparations for dextrorphan were as follows:c_(max)(7±4)vs(7.5±2.9)μg·L~(-1);t_(max)(2.1±0.6)vs(1.9±0.7)h;AUC_(0-24)(38±15)VS(39±12)μg·h·L~(-1);t_(1/2)(6±3)vs(5.1±2.7)h,respectively.The correlative bioavailabilities of paracetamol, pseudoephedrine and dextromethorphan in the test tablet to those of reference tablet were(103±8)%,(100±18)%,(109±26)%,respectively.There were no significant differences in t_(max),c_(max),AUC_(0-t)and AUC_(0-∝) between the two preparations(P>0.05).CONCLUSION The two kinds of paraeetamol,pseudoephedrine and dextromethorphan tabletsⅡpossess bioequivalent.