Limitied Sampling Strategy for Primary Estimation of the Area Under the Curve of Busulfan in HSCT Patients

OBJECTIVE To estimate area under the curve between 0 and 6 h(AUC_{0-360 min}) of busulfan in HSCT patients by limited sampling strategy(LSS). METHODS All of 17 patients were given busulfan by intravenous infusion. At the first agent and the ninth agent, blood samples at different time points before and after drug administration were collected. The blood concentrations of busulfan were determined by a validated HPLC method. The 1-4 sampling points were selected to build limited sampling model, then chose the best model to estimate pharmacokinetic parameters. RESULTS The linear relationship of the model established by 2-4 drug concentration points was ideal. The best regression models of the intravenous infusion first dose were 180, 300 min; 180, 240, 360 min and 120, 150, 180, 240 min. Models of the ninth dose were 120, 240 min; 120, 150, 360 min and 120, 240, 300, 360 min. CONCLUSION To estimate pharmacokinetic parameters of busulfan by intravenous infusion in HSCT patients by limited sampling strategy is feasible. The method can applied in therapeutic drug monitoring.