目的研究缬沙坦氨氯地平片在健康受试者体内的人体药动学和生物等效性。方法采用随机、开放、四周期、两序列完全重复交叉设计,72例受试者(空腹和餐后实验各36例)单次口服受试制剂(T)或参比制剂(R)(含缬沙坦:80 mg;氨氯地平:5 mg)后,采...目的研究缬沙坦氨氯地平片在健康受试者体内的人体药动学和生物等效性。方法采用随机、开放、四周期、两序列完全重复交叉设计,72例受试者(空腹和餐后实验各36例)单次口服受试制剂(T)或参比制剂(R)(含缬沙坦:80 mg;氨氯地平:5 mg)后,采用液相色谱-串联质谱技术(liquid chromatography tandem mass spectrometry,LC-MS/MS)测定人血浆中缬沙坦和氨氯地平浓度。选择Phoenix WinNonlin 8.2计算药动学参数,采用参比制剂校正的平均生物等效性(reference-scaled average bioequivalence,RSABE)或平均生物等效性(average bioequivalence,ABE)方法评价缬沙坦的生物等效性,ABE方法评价氨氯地平的生物等效性。结果空腹和餐后受试者单剂量口服缬沙坦氨氯地平片受试制剂和参比制剂后的平均血药浓度-时间曲线表明本研究受试制剂与参比制剂中缬沙坦、氨氯地平的食物影响与原研药说明书一致。空腹实验缬沙坦C_(max)和AUC_(0-t)的个体内变异系数(coefficient of variation within individuals,CVW)≥30%,用RSABE方法评价两参数的生物等效性,缬沙坦受试制剂和参比制剂C_(max)和AUC_(0-t)的几何均值比(geometric mean ratio,GMR)分别为101.03%、101.86%,且单侧95%置信区间(confidence interval,CI)上限均<0;空腹实验缬沙坦AUC_(0-∞)和氨氯地平C_(max)、AUC_(0-72)以及餐后实验缬沙坦C_(max)、AUC_(0-t)、AUC_(0-∞)和氨氯地平C_(max)、AUC_(0-72)的CVW均<30%,用ABE方法评价各药动学参数的生物等效性,各参数的GMR的90%CI均在80.00%~125.00%等效范围,说明两制剂具有生物等效性。结论缬沙坦氨氯地平片受试制剂和参比制剂药动学参数无明显差异,两制剂生物等效。展开更多
Gold nanoparticles with different morphologies, such as spindle, octahedron, and decahedron were obtained by using different molar ratios of HAuCl4/HEPES in the presence and absence of surfactants at room temperature....Gold nanoparticles with different morphologies, such as spindle, octahedron, and decahedron were obtained by using different molar ratios of HAuCl4/HEPES in the presence and absence of surfactants at room temperature.These nanoparticles were characterized by X-ray diffraction（XRD）, transmission electron microscopy（TEM）, high-resolution transmission electron microscopy（HRTEM）, scanning electron microcopy（SEM）, energy-dispersive X-rays analysis（EDX）, and selected area electron diffraction（SAED）.The kinetics of the formation of gold nanoparticles in HEPES buffer was studied by UV-visible spectrophotometer.The formation of gold nanoparticles was strongly dependent on the concentration of HEPES and pH value.The surfactants play a crucial role in the size and shape controlled synthesis of gold nanoparticles.展开更多
文摘目的研究缬沙坦氨氯地平片在健康受试者体内的人体药动学和生物等效性。方法采用随机、开放、四周期、两序列完全重复交叉设计,72例受试者(空腹和餐后实验各36例)单次口服受试制剂(T)或参比制剂(R)(含缬沙坦:80 mg;氨氯地平:5 mg)后,采用液相色谱-串联质谱技术(liquid chromatography tandem mass spectrometry,LC-MS/MS)测定人血浆中缬沙坦和氨氯地平浓度。选择Phoenix WinNonlin 8.2计算药动学参数,采用参比制剂校正的平均生物等效性(reference-scaled average bioequivalence,RSABE)或平均生物等效性(average bioequivalence,ABE)方法评价缬沙坦的生物等效性,ABE方法评价氨氯地平的生物等效性。结果空腹和餐后受试者单剂量口服缬沙坦氨氯地平片受试制剂和参比制剂后的平均血药浓度-时间曲线表明本研究受试制剂与参比制剂中缬沙坦、氨氯地平的食物影响与原研药说明书一致。空腹实验缬沙坦C_(max)和AUC_(0-t)的个体内变异系数(coefficient of variation within individuals,CVW)≥30%,用RSABE方法评价两参数的生物等效性,缬沙坦受试制剂和参比制剂C_(max)和AUC_(0-t)的几何均值比(geometric mean ratio,GMR)分别为101.03%、101.86%,且单侧95%置信区间(confidence interval,CI)上限均<0;空腹实验缬沙坦AUC_(0-∞)和氨氯地平C_(max)、AUC_(0-72)以及餐后实验缬沙坦C_(max)、AUC_(0-t)、AUC_(0-∞)和氨氯地平C_(max)、AUC_(0-72)的CVW均<30%,用ABE方法评价各药动学参数的生物等效性,各参数的GMR的90%CI均在80.00%~125.00%等效范围,说明两制剂具有生物等效性。结论缬沙坦氨氯地平片受试制剂和参比制剂药动学参数无明显差异,两制剂生物等效。
基金supports from the Program for Excellent Talents of the Department of Education of Hubei Province, China (No. Q20081504)the Area of Excellence Scheme administered by the University Grant Committee and the University of Hong Kong (No.AoE/ P-10/ 01)
文摘Gold nanoparticles with different morphologies, such as spindle, octahedron, and decahedron were obtained by using different molar ratios of HAuCl4/HEPES in the presence and absence of surfactants at room temperature.These nanoparticles were characterized by X-ray diffraction（XRD）, transmission electron microscopy（TEM）, high-resolution transmission electron microscopy（HRTEM）, scanning electron microcopy（SEM）, energy-dispersive X-rays analysis（EDX）, and selected area electron diffraction（SAED）.The kinetics of the formation of gold nanoparticles in HEPES buffer was studied by UV-visible spectrophotometer.The formation of gold nanoparticles was strongly dependent on the concentration of HEPES and pH value.The surfactants play a crucial role in the size and shape controlled synthesis of gold nanoparticles.
