摘要
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。
AIM To study the pharmacokinetics of enalapril-felodipine extended release tablet after a single-dose and multi-dose oral administration in Chinese healthy volunteers, and to evaluate the extended-release characteristics of felodipine in this test combined preparation. METHODS Eleven healthy male volunteers were randomly administered the test and reference formulation preparations in a single-dose and multi- dose, under two-way crossover design. Serum felodipine, enalapril and the active metabolite enalaprilat concentrations were determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the pharmacokinetic parameters were calculated by DAS 2.0 program. RESULTS ρmax,tmas, AUC0-t of test and reference tablets after single dose were as follows : (1.8±s 1.0) vs. (2.2±1.5) μg·L^-1, (8±4) vs. (4.1± 2.0) h, (38 ± 24) vs. (28 ± 22) μg·L^-1 in felodipine; (44 ± 16) vs. (38 ± 12) μg·L^-1, (0.77 ± 0.18) vs. (1.2 ± 0.6) h, (70 ± 22) vs. (76 ± 20)μg·L^-1 in enalapril, and (23 ± 12) vs. (21 ± 9μg·L^-1, (4.4 ±1.1) vs. (4.5 ± 0.9) h, (211 ± 78) vs. (215 ± 79) μg·L^-1 in enalaprilat. The steady state concentrations (p ) and fluctuate degree (DF) of test and reference tablets after multi-dose were as follows: (1.8 ± 1.3) vs. (1.5 ± 0.9) μg·L^-1 and (0.96 ± 0.24) vs. (2.7 ± 1.4) respectively in felodipine, and (10 ± 3) vs. (10 ± 3) μg·L^-1, (2.8 ± 0.5) vs. (2.8 ± 0.5) in enalaprilat. CONCLUSION Comparing with the reference tablet, felodipine in the test combination tablet shows extended release characteristics and the pharmaeokinetic process of enalapril and the active metabolite enalaprilat reveals as basically similar in healthy male volunteers.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2010年第7期519-523,共5页
Chinese Journal of New Drugs and Clinical Remedies
基金
上海市科委科研计划项目(08411966700)
关键词
药动学
依那普利
非洛地平
依那普利拉
色谱法
高压液相
串联质谱法
pharmacokinetics
enalapril
felodipine
enalaprilat
chromatography, high pressure liquid
tandem mass spectrometry