白消安注射液在中国造血干细胞移植患者的生物等效性研究  

Bioequivalence study of busulfan injection in Chinese patients with hematopoietic stem cell transplantation

作　　者：辛向可 石友权 王娜 孟凡凯[1] 万滢 陈琳[1] 郑恒[2] 张义成[1,3] XIN Xiang-ke;SHI You-quan;WANG Na;MENG Fan-kai;WAN Ying;CHEN Lin;ZHENG Heng;ZHANG Yi-cheng(Department of Hematology,Chinese Academy of Medical Sciences,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei Province,China;Department of Pharmacy,Chinese Academy of Medical Sciences,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei Province,China;Key Laboratory of Organ Transplantation,Ministry of Education,National Health Commission Key Laboratory of Organ Transplantation,Key Laboratory of Organ Transplantation,Chinese Academy of Medical Sciences,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei Province,China)

机构地区：[1]华中科技大学同济医学院附属同济医院,血液内科,湖北武汉430030 [2]华中科技大学同济医学院附属同济医院,药学部,湖北武汉430030 [3]华中科技大学同济医学院附属同济医院,器官移植教育部重点实验室,国家卫生健康委员会器官移植重点实验室,中国医学科学院器官移植重点实验室,湖北武汉430030

出　　处：《中国临床药理学杂志》2023年第11期1603-1607,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81873446)。

摘　　要：目的研究2种白消安注射液在中国异基因造血干细胞移植患者的药代动力学特征,并评价其生物等效性及安全性。方法用单中心、随机、开放、双周期、双交叉的试验设计。纳入接受含大剂量白消安为预处理方案的异基因造血干细胞移植患者,每周期静脉输注受试药物或参比药物白消安注射液,剂量为3.2 mg·kg^(-1)·d^(-1),持续静脉给药4 h,用高效液相色谱-串联质谱法测定给药后不同时间点患者血浆中白消安的浓度,用Phoenix WinNonlin 8.1软件计算主要药代动力学参数,评价2种白消安注射液的生物等效性。结果共入组20例患者。受试制剂和参比制剂白消安的主要药代动力学参数如下:C_(max)分别为(3196.00±440.70)和(3002.00±495.01)ng·mL(-1),t_(max)分别为3.85和3.90 h;t_(1/2)分别为(3.07±0.58)和(3.15±0.64)h,AUC_(0-t)分别为(2.32×10^(4)±4943.06)和(2.27×10^(4)±5283.89)ng·mL(-1)·h,AUC_(0-∞)分别为(2.36×10^(4)±4911.89)和(2.32×10^(4)±5273.14)ng·mL(-1)·h。C_(max)、AUC_(0-t)和AUC_(0-∞)的90%置信区间分别为99.72%~114.44%、98.42%~106.16%和98.28%~105.91%。结论2种白消安注射液的主要药代动力学参数相近,安全性良好,具有生物等效性。Objective To study the pharmacokinetic characteristics of two preparations of busulfan in Chinese patients with allogeneic hematopoietic stem cell transplantation,and to evaluate their bioequivalence.Methods Patients receiving allogeneic hematopoietic stem cell transplantation with a large dose of busulfan as a conditioning regimen were enrolled.Single-center,randomized,open,two-period,and double-crossover experimental design was used.Test drug or reference drug busulfan injection was administered intravenously at a dose of 3.2 mg·kg^(-1)·d^(-1) for 4 hours.High performance liquid chromatography tandem mass spectrometry was used to determine the plasma concentrations of busulfan in patients at different time points after administration.Phoenix WinNonlin 8.1 software was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence.Results A total of 20 patients were enrolled.The main pharmacokinetic parameters of busulfan in the plasma of the test drug and the reference drug:C_(max) were(3196.00±440.70)and(3002.00±495.01)ng·mL^(-1);t_(max) was 3.85 and 3.90 h;t_(1/2) was(3.07±0.58)and(3.15±0.64)h;AUC_(0-t) were(2.32×10^(4)±4943.06)and(2.27×10^(4)±5283.89)ng·mL^(-1)·h;AUC_(0-∞)were(2.36×10^(4)±4911.89)and(2.32×10^(4)±5273.14)ng·mL^(-1)·h,respectively.The 90%confidence intervals for the ratios of C_(max),AUC_(0-t),AUC_(0-∞)were 99.72%-114.44%,98.42%-106.16%,98.28%-105.91%,respectively.Conclusion The main pharmacokinetic parameters of the two busulfan preparations are similar,with good safety and bioequivalence.

关 键 词：白消安 药代动力学 异基因造血干细胞移植 生物等效性 

分 类 号：R979.1[医药卫生—药品]