Pharmacokinetics of liposomal busulphan in man

High doses of busulphan are used in conditioning regimens before stem cell transplantation. Great interpatient variations in pharmacokinetics and a co rrelation between toxicity and high systemic exposure of busulphan have bee n shown in several studies. Some authors have suggested therapeutic drug mo nitoring and intravenous busulphan aiming to reduce the conditioning-relate d toxicity, Liposomal busulphan (LBu) might be an alternative to intravenou s administration of high-dose busulphan in conditioning. In the present stu dy, we investigated the pharmacokinetics of LBu in man, Seventeen consecuti ve patients were enrolled in the study. LBu as a single low dose (2 to 8 mg ) was given to 12 patients (six adults and six children). Five patients rec eived two high doses of LBu which replaced the first and the last doses of the conditioning regimen, The high dose of LBu was raised from 0.4 to 0.9 m g/kg, A significant linear correlation (r(2) = 0.928) was found between the dose of LBu and the area under the plasma concentration-time curve (AUC) ( P < 0.001). AUC corrected for 1 mg/kg was 5491 <plus/minus> 912 ng .h/ml an d 5955 +/- 627 ng .h/ml (low dose of LBu in children and adults, respective ly) and 6167 +/- 1385 ng .h/ml and 6933 +/- 656 ng .h/ml (ie the first and the last high doses of LBu, respectively), No significant correlation was f ound between clearance and age or apparent volume of distribution and age ( r(2) = 0.146 and r(2) = 0.046, respectively). No toxicity related to the li posomal formulation of busulphan was observed. We conclude that LBu is suit able for conditioning before stem cell transplantation.