Age-dependent pharmacokinetic profile of single daily dose i.v. busulfan in children undergoing reduced-intensity conditioning stem cell transplant.

Abstract

We studied the pharmacokinetic (PK) profile of single daily dose i.v. BU in children who underwent reduced-intensity conditioning (RIC) transplantation. A cohort of 19 patients < or =4 years of age (group 1) and 33 patients >4 years (group 2) was studied. Patients received a BU test dose for PK studies, followed by two treatment doses adjusted to target an area under the curve (AUC) of 4000 microM min per day. Patients in group 1 attained a lower AUC as compared to group 2 (3568 vs 4035 microM min). In group 1, 67% patients and in group 2, 84% patients achieved AUC within the targeted range. Stable donor chimerism was achieved in 56% patients in group 1 and 79% in group 2. Eight patients required a second transplantation because of graft failure. Because of the concern that a low AUC adversely affected outcomes, a second cohort of 23 patients followed a modified protocol with a targeted AUC of 5000 microM min. A higher AUC was attained (4825 microM min). Stable donor chimerism was achieved in 91% of patients. Our results show that RIC regimens using two single daily doses of i.v. BU are effective in children, but a targeted AUC of 5000 microM min is recommended.

DOI: 10.1038/bmt.2008.437

Cite this paper

@article{Tse2009AgedependentPP, title={Age-dependent pharmacokinetic profile of single daily dose i.v. busulfan in children undergoing reduced-intensity conditioning stem cell transplant.}, author={William T Tse and Reggie E. Duerst and Jennifer Schneiderman and Sonali Chaudhury and David A. Jacobsohn and Morris Kletzel}, journal={Bone marrow transplantation}, year={2009}, volume={44 3}, pages={145-56} }