单剂量口服非洛地平缓释片的药动学及生物等效性

Pharmacokinetics and bioequivalence of felodipine sustained-release tablets after a single dose administration in healthy volunteers

目的研究单剂量口服国产非洛地平缓释片在健康志愿者体内的药动学特征,并评估其与参比制剂之间的生物等效性。方法 20名健康男性志愿者采用两制剂双周期交叉试验设计。以尼莫地平为内标,采用LC-MS/MS法测定血中药物浓度。以BAPP 2.2计算其药动学参数,评价受试制剂与参比制剂之间的生物等效性。结果 20名受试者单剂量口服10 mg受试制剂和参比制剂后非洛地平的主要药动学参数ρ_(max)分别为(3.09±1.03)μg·L^(-1)和(2.68±0.88)μg·L^(-1);t_(max)分别为(3.8±1.0)h和(3.5±1.4)h;t_(1/2)分别为(14.49±2.72)h和(13.74±3.42)h;MRT为(19.87±2.62)h和(19.08±4.73)h;AUC_(0→48)为(30.83±6.04)μg·h·L^(-1)和(31.42±5.78)μg·h·L^(-1);AUG_(0→∞)为(34.00±5.76)μg·h·L^(-1)和(34.93±6.54)μg·h·L^(-1)。受试制剂与参比制剂的主要药动学参数经统计学分析无明显差异。受试制剂的相对生物利用度为(98.5±11.0)%。结论国产非洛地平缓释片与其参比制剂之间具有生物等效性。

AIM To investigate the pharmacokinetic properties and bioequivalence of felodipine sustained-release tablets after a single dose administration in healthy volunteers.METHODS The study was designed in a two-treatment, two-period,two-sequence randomized cross-over trial.Plasma concentrations were determined by LC-MS/MS method. Nimodipine was used as the internal standard.RESULTS The main pharmacokinetic parameters were calculated by BAPP 2.2 software and the bioequivalence were compared.The main pharmacokinetic parameters were as follows：ρmax） were（3.09±1.03）μg·L^-1 and（2.68±0.88）μg·L^-1;tmax were（3.8±1.0）h and（3.5±1.4）h;t1/2 were （14.49±2.72）h and（13.74±3.42）h;MRT were（19.87±2.62）h and（19.08±4.73）h;AUC0→48 were（30.83±6.04）μg·h·L^-1 and（31.42±5.78）μg·h·L^-1;AUC0→∞ were（34.00±5.76）μg·h·L^-1 and（34.93±6.54）μg·h·L^-1,respectively.The relative bioavailability of tested tablets was（98.5±11.0）%.CONCLUSION The test and reference preparations are bioequivalent.