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目的研究依那普利非洛地平缓释片在中国健康人体内的药动学,并考察制剂中非洛地平的缓释特征。方法 11名健康男性受试者随机双交叉单次及多次口服依那普利非洛地平缓释片受试制剂和参比制剂,采用液相色谱-串联质谱(LC-MS/MS)法测定血清中非洛地平、依那普利及其活性代谢物依那普利拉的浓度,用DAS2.0软件计算药动学参数。结果受试者单次服用受试制剂和参比制剂后,非洛地平的ρ_(max)、t_(max)、AUC_(0～t)分别为(1.8±s 1.0)和(2.2±1.5)μg·L~(-1),(8±4)和(4.1±2.0)h,(38±24)和(28±22)μg·h·L~(-1);依那普利的相应参数分别为(44±16)和(38±12)μg·L~(-1),(0.77±0.18)和(1.2±0.6)h,(70±22)和(76±20)μg·h·L~(-1);依那普利拉的相应参数分别为(23±12)和(21±9)μg·L~(-1),(4.4±1.1)和(4.5±0.9)h,(211±78)和(215±79)μg·h·L~(-1)。受试者多次服用受试制剂和参比制剂后,非洛地平的稳态血药浓度(ρ_(ss-av))和波动系数(DF)分别为(1.8±1.3)和(1.5±0.9)μg·L~(-1),(0.96±0.24)和(2.7±1.4);依那普利拉则为(10±3)和(10±3)μg·L~(-1),(2.8±0.5)和(2.8±0.5)。结论与参比制剂相比,受试制剂中的非洛地平具有缓释片的生物学特征,依那普利及其活性代谢物依那普利拉在健康男性受试者体内的药动学过程基本一致。
Objective To study the pharmacokinetics of enalapril and felodipine sustained-release tablets in Chinese healthy volunteers and investigate the sustained-release characteristics of felodipine in the preparation. Methods Eleven healthy male subjects were randomized to double crossover oral single or multiple oral enalapril felodipine sustained-release tablets and reference preparations. Liquid chromatography-tandem mass spectrometry (LC-MS / MS) The concentrations of felodipine, enalapril and enalapril, their active metabolites, were determined in serum and pharmacokinetic parameters were calculated using the DAS 2.0 software. Results After a single dose of test and reference preparations, the ρ max, t max and AUC 0 t of felodipine were (1.8 ± s 1.0) and (2.2 ± 1.5), respectively, μg · L -1, (8 ± 4) and (4.1 ± 2.0) h, (38 ± 24) and (28 ± 22) μg · h · L -1, The parameters were (44 ± 16) and (38 ± 12) μg · L -1, (0.77 ± 0.18) and (1.2 ± 0.6) h, (70 ± 22) and (76 ± 20) μg · h · L ~ (-1) and enalaprilat were (23 ± 12) and (21 ± 9) μg · L -1, (4.4 ± 1.1) and (4.5 ± 0.9) h respectively , (211 ± 78) and (215 ± 79) μg · h · L -1, respectively. The steady-state blood concentration (ρ_ (ss-av)) and fluctuation coefficient (DF) of felodipine were (1.8 ± 1.3) and (1.5 ± 0.9 ) (μg · L -1, (0.96 ± 0.24) and (2.7 ± 1.4)) and enalapril (10 ± 3) and (10 ± 3) μg · L -1 2.8 ± 0.5) and (2.8 ± 0.5). Conclusion Compared with the reference formulation, the felodipine in the test preparation has the biological characteristics of sustained release tablets. The pharmacokinetics of enalapril and its active metabolite enalaprilat in healthy male subjects The process is basically the same.