摘要
建立了高灵敏度的LC-MS/MS法检测人血浆中骨化三醇的含量,定量下限达到20 pg/mL,能够满足临床检测的需求。采用随机、开放、三周期、三交叉的试验设计,对骨化三醇的受试制剂与市售参比制剂在36名中国健康志愿者体内的药动学特征进行比较,考察二者的生物等效性。健康志愿者空腹单次口服给予骨化三醇软胶囊(4.0μg),受试制剂与参比制剂的主要药动学参数t_(max)分别为(3.46±1.33)和(2.92±1.47)h;t_(1/2)分别为(8.14±3.22)和(7.70±2.32)h;c_(max)分别为(160.68±52.41)和(169.00±50.26)pg/mL。并且,受试制剂与参比制剂的血浆药物浓度变化趋势一致,主要药动学参数几何均值比90%置信区间均在80.00%~125.00%,表明受试制剂与参比制剂具有生物等效性。
A highly sensitive LC-MS/MS method was established for detecting calcitriol content in human plasma,with a lower limit of quantification of 20 pg/mL,which could meet the clinical detection needs.A randomized,open,three cycles,triple crossover design was used to investigate and compare the pharmacokinetic characteristics and bioequivalence between the tested preparation and the commercially available reference preparation of calcitriol in 36 healthy Chinese volunteers who were given a single oral administration of calcitriol soft capsules(at a dose of 4.0μg)on an empty stomach.The results showed that the main pharmacokinetic parameters of the tested preparation and the reference preparation were as follows:t_(max)were(3.46±1.33)and(2.92±1.47)h,t_(1/2)were(8.14±3.22)and(7.70±2.32)h,c_(max)were(160.68±52.41)and(169.00±50.26)pg/mL,respectively.The variance in plasma concentrations of the tested and the reference preparations showed the same trend.The geometric mean ratios of the main pharmacokinetic parameters were within the 90%confidence interval of 80.00%-125.00%,indicating that the test and reference formulations were bioequivalent.
作者
钱红
边静
陈阳生
杜昌余
张怀征
徐智儒
QIAN Hong;BIAN Jing;CHEN Yangsheng;DU Changyu;ZHANG Huaizheng;XU Zhiru(China State Institute of Pharmaceutical Industry,Shanghai 201203;National Key Lab.of Lead Druggability Research,Shanghai Institute of Pharmaceutical Industry Co.,Ltd.,Shanghai 200437;Shanghai Professional and Technical Service Center for Biological Material Druggability Evaluation,Shanghai 200437;Qingdao Chia Tai Haier Pharmaceutical Co.,Ltd.,Qingdao 266071)
出处
《中国医药工业杂志》
EI
CAS
CSCD
2024年第9期1236-1243,共8页
Chinese Journal of Pharmaceuticals
作者简介
钱红(1997-),女,硕士研究生,专业方向:药物代谢动力学;通信作者:徐智儒(1978-),女,博士,研究员,从事药物代谢动力学研究。E-mail:xuzhiru@sinopharm.com。
