ABSTRACT
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 AUC0-6, 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 AUC0-6 accurately (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 AUC0-6 produced by the classical method. CONCLUSION: The proposed limited sampling strategy to estimate AUC0-6 based on C2 and C5 can be used to busulfan blood concentration monitoring in clinical practice.