多剂量口服硝苯地平缓释片的药动学及生物等效性

Pharmacokinetics properties and bioequiavailability of nifedipine sustained-release tablets after multiple doses administration in healthy volunteers

目的:研究多剂量口服硝苯地平缓释片在人体内的药动学特点和国产硝苯地平缓释片的生物等效性.方法:健康志愿受试者20名,口服硝苯地平试验品和参比品20mg,用标准二阶段交叉设计自身对照试验方法,采用液相色谱串联质谱方法(LC-MS/MS)测定服药后不同时刻的血药浓度,计算主要药动学参数,并采用方差分析和双单侧t检验(1-2a)90%置信区间进行生物等效性评价.结果:受试者分别口服受试品和参比品后,其主要药动学参数Tmax,Cmax,T1/2和AUCss分别为:(4.10±1.07),(4.55±1.23)h;(52.64±15.80),(51.54±12.87)μg/L;(8.44±1.69),(8.33±2.27)h;(352.96±85.12),(367.96±71.28)ng/(h·mL);受试品的相对生物利用度为(96.2±17.3)%.结论:硝苯地平缓释片和硝苯地平缓释片(1)制剂具有生物等效性.

AIM：To investigate the pharmacokinetics properties and bioequiavailability of nifedipine sustained-release tablets after multiple doses administration in healthy volunteers. METHODS：An open,randomized and two-period crossover study with a 2-week washout interval was performed in 20 healthy volunteers. Concentrations of nifedipine in plasma were assayed by LC-MS/MS spectrometric method after multiple doses of 20 mg of the tested or the referenced tablets. The pharmacokinetics parameters,Tmax,Cmax,T1/2 and AUCss were analyzed by two one-side t test and （1-2 a ）90%. RESULTS：The main pharmacokinetics of the tested and referenced tablets were：Tmax：（4.10±1.07） and （4.55±1.23） h; Cmax：（52.64±15.80） and （51.54±12.87） ng /mL; T1/2：（8.44±1.69） and （8.33±2.27） h; and AUCss：（352.96±85.12） and （367.96 ± 71.28） ng/（h·mL）. The relative bioavailiability of nifedipine was （96.2±17.3）%. CONCLUSION：The results of the statistical analysis shows that the two formulations are bioequivalent.