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Limited Sampling Strategies for Clinical Plasma Concentration Monitoring of Busulfan in Hematopoietic Stem Cell Transplantation Patients

??OBJECTIVE To establish limited sampling strategy to estimate area under the curve (AUC) of HSCT patients who had received busulfan (Bu) intravenous infusion. METHODS Plasma samples were collected at certain time points from 22 HSCT patients who had received busulfan intravenous infusion. The LC-MS/MS method was used to measure blood concentration of busulfan. The classical method was used to calculate pharmacokinetic parameters. To estimate AUC_0-6, measured blood concentration data was used to build a multiple linear regression model which was subsequently validated. Consistency between results produced by the traditional method and the proposed LSS respectively was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. RESULTS It is shown that model based on concentrations on two sampling time points (2 and 5 h) is able to predict AUC_0-6accurately (adjusted r²=0.917. MPE=0.2%, RMSE=4.48%). The 95% confidence interval of ICC is 0.914-0.984 while the limit of agreement in the BA is -0.9-8.8. Results produced by limited sampling strategy are nearly consistent with AUC_0-6 produced by the classical method. CONCLUSION The proposed limited sampling strategy to estimate AUC_0-6 based on C₂ and C₅ can be used to busulfan blood concentration monitoring in clinical practice.