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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 pharmacokinetics of high-dose buprofezin (Bu) in patients with allo-HSCT preconditioning. Methods Allo-HSCT pretreatment oral Bu1mg · kg-1, q6h, a total of 16 doses. When the first dose and the ninth dose were administered, the blood samples were taken before administration and at different time points after administration, respectively. The concentration of plasma Bu was measured by HPLC. Pharmacokinetic model was fitted by DAS software, Pharmacokinetic parameters were calculated. Results The concentration-time curves of Bu in the allo-HSCT pretreated group were consistent with the one-compartment model after the first dose and the ninth dose of bu and the main pharmacokinetic parameters were: t1 / 2 (133.0 ± 30.6) and ( (0.56 ± 0.12) and (0.46 ± 0.08) L · kg-1, respectively, with CL / F (0.003 ± 0.001) and Ke (0.005 ± 0.001) and (0.006 ± 0.001) min- AUC0-t (910.3 ± 146.9) and (1158.5 ± 139.0) μmol · min · L-1, AUC0-∞ (1401.9 ± 243.2) and (1689.0 ± 312.4) μmol · min · L-1; mean steady-state plasma concentration of Bu was (3.29 ± 0.39) μmol·L-1. Conclusion The oral administration of high-dose Bu in allo-HSCT pretreated patients consistent with one-compartment pharmacokinetic model, the main pharmacokinetic parameters of individual differences, after repeated administration of drug clearance changes.