曲马氨酚片的人体药物动力学研究

摘要

To stury the pharmacokinetie of tramadol and aeetaminophen in healthy volunteers. Methods Totally 20 healthy adult male volunteers participated in the study were randomly assigned to 2 treatment groups and were given respectively the dose of one and two pills by oral administration. Serum was separated and the concentrations of tramadol and acetaminophen in human serum were determined by HPLC using fluorescence and UV detector. The values of concentration were directly detected, and AUC was calculated by linear trapezoid method. Results The main pharmacokinetie parameters of tramadol and acetaminophen of 2 dosages groups were as follow: Tramadol: AUC_(0-24h)(ng · h· mL~(-1)) were 2 724. 89 ± 1 016.54 and 1 361.61 + 441. 79; AUC_(0-∞)(ng·h·mL~(-1)) were3 065.49±1 190.66 and 1 555.04±582.51; t_(max)(h) were 1.8±0.75 and 1.9±0.57; t_(t/2)(h) were 7.34±1.39and7.63±2.02; Kel(h~(-1)) were 0. 098±0. 019 and 0. 097± 0.027; Cl_r(mL · min~(-1)) were 31.84±13.65 and 30.03 ± 9.20; MRT(h) were 7.62 ± 1.07 and 7.77 ± 0.75. Acetaminophen. AUC_(0-24h)(μg · h · mL~(-1)) were 40.28 ± 10.36 and 18.37 ± 3.84 ; AUC_(0-∞)(μg · h · mL~(-1)) were 41.63 ± 10. 96 and 18. 81 ± 4.06; t_(max)(h) were 0. 9 ± 0.46 and 0. 9 ± 0. 39; t_(t/2)(h) were5.39 ± 1. 16 and 4. 96 ± 1.03; Kel(h~(-1)) were 0. 13 ± 0. 03 and 0. 15 ± 0. 03; Clr (mL · min~(-1)) were 17.17 ± 4.57 and 18.42 ± 3.89; MRT(h) were 4.86 ± 0.48 and 4.50 ± 0.53. Conclusions No significant difference in pharmacokinetic parameters, such as t_(max), t_(t/2), Ke,Cl, MRT,AUC_(0-t)/dose, AUC_(0-∞)/dose and C_(max)/dose are shown between these two dose groups and a linear pharmacokinetic is featured.%目的 测定曲马氨酚片中曲马多和对乙酰氨基酚的药动学参数.方法 采用高效液相色谱法分别测定20名健康志愿者口服曲马氨酚片(2个剂量组:1片和2片,每组10名)后血清中的药物浓度,进行药动学分析.结果 2组健康志愿者口服曲马氨酚片后的主要药动学参数:曲马多AUC_(0-24h)(ng·h·mL~(-1))分别为2 724.89±1 016.54,1 361.61±441.79;AUC_(0-∞)(ng·h·mL~(-1))分别为3 065.49±1 190.66,1 555.04 ± 582.51;t_(max)(h)分别为1.8±0.75,1.9±0.57;t_(1/2)(h)分别为7.34±1.39,7.63±2.02;Kel(h~(-1))分别为0.098±0.019,0.097 ± 0.027;Clr(mL·min~(-1))分别为31.84±13.65,30.03±9.20;MRT(h)分别为7.62±1.07,7.77±0.75.对乙酰氨基酚的AUC_(0-24h)(μg·h·mL~(-1))分别为40.28±10.36,18.37±3.84;AUC_(0-∞)(μg·h·mL~(-1))分别为41.63±10.96,18.81±4.06;t_(max)(h)分别为0.9±0.46,0.9±0.39; t_(1/2)(h)分别为5.39±1.16,4.96±1.03;Kel(h~(-1))分别为0.13±0.03,0.15±0.03;Clr(mL·min~(-1))分别为17.17±4.57,18.42±3.89;MRT(h)分别为4.86±0.48,4.50±0.53.结论 各剂量组之间的主要药动学参数(t_(max),t_(1/2),Kel,Clr,Vd,MRT)无显著性差异,各剂量组AUC_(0-t)/dose,AUC_(0-∞)/dose,C_(max)/dose比较无显著性差异;符合线性动力学特征.