复方氨酚右敏溶液在健康人体的药代动力学研究

PHARMACOKINETICS OF PARACETAMOL AND DEXCHLORPHENIRAMINE MALEATE ORAL SOLUTION IN HEALTHY VOLUNTEERS

研究复方氨酚右敏溶液在健康人体的药代动力学．12名健康受试者以自身为对照采用随机交叉给药方式，单次空腹I：1服3个剂量复方氨酚右敏溶液（低、中、高3个剂量分别为7．5、15、30mL，每mL含对乙酰氨基酚32mg、马来酸右氯苯那敏0．1mg）．用液相色谱-串联质谱法（LC-MS／MS）测定血浆中对乙酰氨基酚和马来酸右氯苯那敏的浓度，计算2种药物的药代动力学参数，评价其药代动力学特征．对乙酰氨基酚在人体内的动力学过程符合二室模型，低、中、高3个剂量主要药代动力学参数消除半衰期t1／2分别为（2．93±0．47）、（3．08士0．43）、（3．01±0．49）h，血药质量浓度-时间曲线下面积AUC0～t，分别为（12．29±3．91）、（27．80±7．64）、（60．41±17．24）μg·h·mL^-1；右氯苯那敏在人体内的动力学过程符合一室模型，低、中、高3个剂量主要药代动力学t1／2分别为（20．49±7．86）、（19．66±5．05）、（19．96±6．48）h；AUC0～t，分别为（32．61±13．65）、（67．58±23．31）、（158．12±56．44）ng·h·mL^-1．对乙酰氨基酚和右氯苯那敏药动学参数ρmax、AUC0～t、AUC0-∞均与给药剂量呈线性相关（P〈0．001），复方氨酚右敏溶液在7．5～30mL剂量范围内呈线性人体药代动力学特征．

To study the pharmacokinetics of paracetamol and dexchlorpheniramine maleate oral solution in healthy volunteers. A single oral dose of three dosage levels （7.5, 15 and 30 mL （paracetamol 32 mg and dexchlorpheniramine maleate 0.1 mg per 1 mL oral solution）） were given to each volunteer according to an open randomized crossover design. The concentration of paracetamol and dexchlorpheniramine in plasma was determined by LC-MS/MS. The pharmacokinetic parameters were determined. Plasma concentration curves of paracetamol conformed to two compartment model. The main pharmacokinetic parameters of paracetamol for three dosage levels were as follows, t1/2 were （2.93±0.47）, （3.08±0. 43）, （3.01±0. 49） h; AUC0-t, were （12.29±3.91）,（27.80±7.64）,（60.41±17.24）g·h·mL^-1; Plasma concentration curves of dexchlorphe- niramine conformed to one compartment model. The main pharmacokinetic parameters of dexchlorpheniramine for three dosage levels were as follows, h1/2 were （20.49±7.86）,（19.66±5.05）,（19.96±6.48） h; AUC0-t were （32.61±13.65） ,（67.58±23.31）, （158.12±56.44） ng·h·mL^-1. The main pharmacokinetic parameters Pmax, AUC0-t and AUC0-∞ of paracetamol and dexchlorpheniramine showed linear correlation to dosage （P〈0.001）. Paracetamol and dexchlorpheniramine maleate oral solution showed linearity pharmacokinetics in 7.5-30 mL dosages in healthy volunteers.