国产复方阿米三嗪片人体生物等效性研究

BIOEQUIVELENCE OF COMPOUND ALMITRINE TABLETS IN HEALTHY VOLUNTEERS

10名健康志愿者随机交叉给药,分别口服150mg来考察国产与进口复方阿米三嗪片进行相对生物利用度研究。采用高效液相色谱法测定血浆中阿米三嗪和萝巴新的浓度,经3P97程序处理拟合,两者皆符合口服给药二室开放模型,国产与进口两种片剂中阿米三嗪的AUC分别为35008.75±2577.14μg·h·L-1 和34174.91±2335.17μg·h·L-1,Tmax 分别为3.64±0.66h和3.81±0.76h ,Cmax 分别为830.31±77.97μg·L -1和816.76±70.07μg·L -1;国产与进口两种片剂中萝巴新AUC分别为1141.99±116.69μg·h·L-1 和1116.15±81.85μg·h·L-1,Tmax 分别为1.25±0.24h和1.27±0.22h,Cmax 分别为385.17±86.26μg·L -1和374.04±71.71μg·L -1 ,经配对t-检验,阿米三嗪和萝巴新在两种片剂中的各药代动力学参数均无显著性差异(P>0.05)。用梯形法计算国产与进口片中阿米三嗪的AUC0 -t 分别为32429.35±3324.41μg·h·L -1和31334.65±2982.17μg·h·L -1,萝巴新的AUC0 -t 分别为1176.55±148.96μg·h·L -1和1145.44±119.25μg·h·L-1,国产复方阿米三嗪的相对生物利用度为103.53%±5.00 %(阿米三嗪)和102.68%±6.38 %(萝巴新)。对两制剂中阿米三嗪和萝巴新梯形法计算的AUC0 -t 及实测的Cmax 、Tpeak 进行方差分析。

A single oral domestic compound domestic and imported almitrine tablets and to 10 healthy male volunteers in a randomized cross-over studied. Plasma concentrations of almitrine and raubasine were determined with high-performance liquid chromatography. The concentration-time curves of almitrine and raubasine fitted into a 2-compartment model. The pharmacokinetic parameters of two formulations for almitrine were:AUC: 35008.75±2577.14 μg·h·L-1 and 34174.91±2335.17 μg·h·L-1, Tmax: 3.64±0.66h and 3.81±0.76 h,Cmax:830.31±77.97 μg·L-1 and 816.76±70.07 μg·L-1.The pharmacokinetic parameters of two formulations for raubasine were: AUC:1141.99±116.69 μg·h·L-1 and 1116.15±81.85 μg·h·L-1, Tmax: 1.25±0.24 h and 1.27±0.22 h,Cmax:385.17±86.26 μg·L-1 and 374.04±71.71 μg·L-1 . Trapezoidal methods caculated AUC0-t of two formalations were: 32429.35±3324.41 μg·h·L-1 and 1334.65±2982.17 μg·h·L-1 (almitrine); 1176.55 μg·h·L-1±148.96 and 145.44±119.25 μg·h·L-1 (raubasine). No statistical different were observed between these two formulations, and the relatives bioavailability of compound almitrine tablets were 103.53%±5.00% for almitrine and 102.68%±6.38% for raubasine. The results demonstrated that two formulations were bioequivalent by t-test, analysis of variance and two one sided tests.