http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16400337&dopt=Abstract

Bone Marrow Transplant. 2006 Feb;37(4):345-51.

Population pharmacokinetics of intravenous busulfan in
patients undergoing hematopoietic stem cell transplantation.

Takama H, Tanaka H, Nakashima D, Ueda R, Takaue Y.

1Product Development Department, Pharmaceutical Division, Kirin Brewery
Company Ltd, Shibuya-ku, Tokyo, Japan.

A population pharmacokinetic analysis was performed in 30 patients who
received an intravenous busulfan and cyclophosphamide regimen before
hematopoietic stem cell transplantation. Each patient received 0.8
mg/kg as a 2 h infusion every 6 h for 16 doses. A total of 690
concentration measurements were analyzed using the nonlinear mixed
effect model (NONMEM) program. A one-compartment model with an additive
error model as an intraindividual variability including an
interoccasion variability (IOV) in clearance (CL) was sufficient to
describe the concentration-time profile of busulfan. Actual body weight
(ABW) was found to be the determinant for CL and the volume of
distribution (V) according to NONMEM analysis. In this limited study,
the age (range 7-53 years old; median, 30 years old) had no significant
effect on busulfan pharmacokinetics. For a patient weighting 60 kg, the
typical CL and V were estimated to be 8.87 l/h and 33.8 l,
respectively. The interindividual variability of CL and V were 13.6 and
6.3%, respectively. The IOV (6.6%) in CL was estimated to be less than
the intraindividual variability. These results indicate high
interpatient and intrapatient consistency of busulfan pharmacokinetics
after intravenous administration, which may eliminate the requirement
for pharmacokinetic monitoring.Bone Marrow Transplantation (2006) 37,
345-351. doi:10.1038/sj.bmt.1705252; published online 9 January 2006.

PMID: 16400337 [PubMed – in process]