摘要
目的研究异基因造血干细胞移植(allo-HSCT)预处理患者口服大剂量白消安(Bu)的药动学特征。方法allo-HSCT预处理患者口服Bu1mg·kg-1,q6h,共16剂。在首剂和第9剂给药时,分别于给药前及给药后不同时间点采集血样,用高效液相色谱法测定血浆Bu浓度;用DAS软件进行药动学房室模型拟合,计算药动学参数。结果首剂和第9剂给药后Bu在allo-HSCT预处理患者体内血药浓度-时间曲线均符合一室模型,其主要药动学参数分别为:t1/2(133.0±30.6)与(131.4±28.2)min,Ke(0.005±0.001)与(0.006±0.001)min-1,Vd/F(0.56±0.12)与(0.46±0.08)L·kg-1,CL/F(0.003±0.001)与(0.002±0.001)L·min-1·kg-1,AUC0-t(910.3±146.9)与(1158.5±139.0)μmol·min·L-1,AUC0-∞(1401.9±243.2)与(1689.0±312.4)μmol·min·L-1;Bu平均稳态血浆浓度为(3.29±0.39)μmol·L-1。结论口服大剂量Bu在allo-HSCT预处理患者体内过程符合一室药动学模型,主要药动学参数个体差异大,多次给药后药物清除率发生改变。
OBJECTIVE To study the pharmacokinetic profiles of oral busulfan in Chinese patients undergoing allogeneic hematopoietic stem cell transplantation. METHODS Blood samples of 9 adult patients were collected following the first and the ninth dose of standard 16 doses of oral busulfan, 4-day regimen. The plasma concentrations of busulfan were determined by HPLC, and the pharmacokinetic parameters of busulfan were calculated by DAS statistical software. RESULTS The plasma concentrationtime curves after dose 1 and dose 9 of oral 1 mg·kg^-1 busulfan in 9 patients were described by an one-compartment model, respectively. The main pharmacokinetic parameters were as follows: t1/2 (133.0±30.6) and (131.4±28.2) min, Ke (0.005±0.001) and (0.006±0.001)min^-1, Vd/F (0.56±0.12) and (0.46±0.08) L·kg^-1, CL/F (0.003±0.001) and (0.002± 0.001 ) L·min^-l·kg^-1, AUC0-t (910.3 ± 146.9) and ( 1 158.5±139.0) μmol·min·L^-1, AUC0_∞ ( 1 401.9±243.2) and ( 1 689.0±312.4) μmol·min·L^-1, respectively. Busulfan average steady state plasma concentration was (3.29±0.39) μmol·L^-1. CONCLUSION The pharmacokinetic profiles of oral busulfan are fitted to an one-compartment model, and the main pharmacokinetic parameters are significant difference between dose 1 and dose 9.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2009年第18期1416-1419,共4页
Chinese Pharmaceutical Journal
基金
安徽高校省级自然科学研究项目(KJ2007B317ZC)
关键词
白消安
异基因造血干细胞移植
预处理方案
药动学
busulfan
allogeneic hematopoietic stem cell transplantation
preparative regimen
pharmacokinetics