Estimation model for exposure of intravenous busulfan in patients receiving autologous hematopoietic stem cell transplantation
- VernacularTitle:干细胞移植患者白消安暴露量的估算模型研究
- Author:
Jin-Wen LI
1
;
Yan XU
;
Xiao-Dan WANG
;
Ying-Xi LIAO
;
Shuai HE
;
Shan XU
;
Ping ZHANG
;
Wen-Juan MIAO
Author Information
- Keywords: busulfan; limited sampling strategy; Jackknife; Bootstrap; autologous stem cell transplantation; AUC; therapeutic drug monitoring
- From: Chinese Pharmacological Bulletin 2024;40(6):1193-1198
- CountryChina
- Language:Chinese
- Abstract: Aim To establish limited sampling strategy to esti-mate area under the drug concentration versus time curve(AUC0-t)of lymphoma patients treated with autologous stem cell transplantation(ASCT)who had busulfan intravenous infu-sion.Methods Twelve lymphoma patients treated with ASCT received a conditioning regimen containing busulfan 105 mg·m-2,Ⅳ infusion for 3 h.Blood samples were obtained 1 h after the start of the first dose of the busulfan infusion,at 5 min,1 h,2 h,4 h,6 h and 18 h after the end of the drug administration.LC-MS/MS was used to determine the busulfan serum concentra-tion.After obtaining the clinical pharmacokinetic parameters of busulfan by traditional pharmacokinetic method,multiple linear stepwise regression analysis was used to establish the AUC0-t es-timation model of busulfan based on limited sampling method.The model was further verified by Jackknife and Bootstrap meth-od.Bland-Altman plots were used to evaluate the consistency between the limited sampling method and the classical pharma-cokinetic method.Results The multiple linear regression equa-tion analysis of C60min,C180min and C300min was obtained by the limited sampling method.The regression equation was AUC0-t=295.003C60min+233.050C180min+273.163C300min-1202.713,r2=0.995,MPE=-0.87％,RMSE=2.40％.Conclusion The limited sampling model with three-point estimation can be used to estimate the AUC0-t of busulfan exposure in lymphoma patients with ASCT to provide reference for clinical application of busulfan.
