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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。
Objective To study the pharmacokinetic characteristics of a single oral dose of domestic felodipine sustained-release tablets in healthy volunteers and evaluate its bioequivalence with reference formulation. Methods Twenty healthy male volunteers were enrolled in a two-cycle crossover design. Taking nimodipine as internal standard, the concentration of blood drug was determined by LC-MS / MS. The pharmacokinetic parameters were calculated using BAPP 2.2 and the bioequivalence between test and reference preparations was evaluated. Results The main pharmacokinetic parameters ρ max of felodipine were (3.09 ± 1.03) μg · L -1 and (2.68) in 20 subjects after oral administration of 10 mg of test compound and reference formulation respectively ± 0.88) μg · L -1; t max was (3.8 ± 1.0) h and (3.5 ± 1.4) h respectively; t 1/2 was (14.49 ± 2.72) h and (13.74 ± (30.83 ± 6.04) μg · h · L -1, and (31.42 ± 5.78) μg · L -1 for AUC_ (0 → 48) h · L ~ (-1); AUG_ (0 → ∞) were (34.00 ± 5.76) μg · h · L ~ (-1) and (34.93 ± 6.54) μg · h · L ~ (-1) respectively. The main pharmacokinetic parameters of the test preparation and the reference preparation showed no significant difference by statistical analysis. The relative bioavailability of the test preparation was (98.5 ± 11.0)%. Conclusion The domestic felodipine sustained-release tablets have bioequivalence with their reference preparations.