Monitoring of busulfan area under the curve: estimation by a single measurement.

Because the busulfan area under the concentration-time curve (AUC) has been correlated with the outcome of bone marrow transplantation (BMT) and the occurrence of veno-occlusive disease after BMT, a rapid determination of AUC is needed to ensure its suitable dosage. The present work describes a method based on combining aliquots from the 10 blood samples collected for an AUC busulfan determination and performing a single determination of the resulting mixture. In 42 patients undergoing a preparative regimen for bone marrow transplantation this combined sample AUC was compared with the regular determined AUC obtained from 10 consecutive samples drawn at various time intervals after dosing. It is apparent that the AUCs calculated by pharmacokinetic analysis using a noncompartmental model package and those obtained by analyzing the sample mixture are very similar ( r = 0.961). The proposed method allows rapid adjustment of the busulfan dose, reducing the number of uncorrected dosages during therapy.