硝苯地平缓释片在健康志愿者体内的生物等效性

Bioequivalent study of nifedipine sustained-release tablets in healthy volunteers

目的建立测定人血浆样品中硝苯地平浓度的LC-MS方法,并应用于硝苯地平缓释片的人体生物等效性研究。方法20名男性健康受试者交叉口服单剂量和多剂量受试制剂或参比制剂,以地西泮为内标,血浆样品经液-液萃取后,测定血药浓度,计算药动学参数和相对生物利用度,评价两制剂的生物等效性。结果单剂量口服受试制剂与参比制剂的主要药动学参数:t_(max)分别为(2.2±0.7)和(2.3±0.8)h;ρ_(max)分别为(68.3±23.2)和(71.1±18.6)μg·L^(-1);t_(1/2)分别为(6.0±2.1)和(6.2±3.4)h;受试制剂的相对生物利用度为(97.5±15.6)%。多剂量口服受试制剂与参比制剂的主要药动学参数(稳态时):t_(max)分别为(2.0±0.8)和(2.2±0.9)h;ρ_(max)分别为(63.1±26.8)和(63.5±2,4.7)μg·L^(-1);t_(1/2)分别为(7.1±2.6)和(7.2±2.6)h;受试制剂的相对生物利用度为(97.1±30.5)%。结论本方法准确可靠,操作快速、简便。受试制剂与参比制剂生物等效。

AIM To develop a LC-MS method for determining the nifedipine in human plasma. The pharmaeokineties and bioequivalenee of nifedipine sustained-release tablets were studied. METHODS The human plasma samples were obtained at certain time points after a single or multiple oral dose of the test or reference formulations. Plasma samples were processed by liquid-liquid extraction using diazepam as the internal standard. The phannaeokinetie parameters were calculated and the bioequivalenee of nifedipine sustained-release tablets were evaluated. RESULTS The main pharmaeokinetie parameters of nifedipine test and reference formulations after a single oral administration were as follows： tmax（2.2±0.7） and （2.3 ±0.8）h;ρmax（68.3 ±23.2）and（71.1 ± 18.6）μg·L^-16.0± 2.1） and （6.2±3.4） h.The relative bioavailability of nifedipine sustained-release tablets was （97.5 ±15.6） %. The main phannaeokinetie parameters after a multiple oral administration were as follows： tmax（2.0 ±0.8） and （2.2 ±0.9） h;ρmax（63.1 ± 26.8） and （63.5± 24.7）μg·L^-1 ; t 1/2 （7.1 ± 2.6） and （7.2 ±2.6） h. The relative bioavailability of nifedipine sustained-release tablets was （97.1 ± 30.5）%. CONCLUSION Tne developed LC-MS method is reliable, rapid and simple. Tne statistical analysis results show that the two formulations are bioequivalent.