Population Pharmacokinetics of Oral Busulfan in Young Japanese Children Before Hematopoietic Stem Cell Transplantation

• DOI: 10.1097/ftd.0b013e3181621cde
• Publication Date: 2009-03-05T06:58:38Z
• Authors: Hiroyoshi Nakamura; Takeyuki Sato; Kenji Okada; Go Miura; Noritaka Ariyoshi; Kazuyoshi Nakazawa; Mitsukazu Kitada
• Keywords: NONMEM

The objectives of this study were to develop a population pharmacokinetic model and determine the covariates affecting pharmacokinetics busulfan in Japanese pediatric patients who received high-dose oral as conditioning regimen before hematopoietic stem cell transplantation. Population analysis was performed using retrospective therapeutic drug monitoring data (including test dose data) from 103 children. Their ages ranged 2 months 11 years old (mean age, 30 months; median 18 months). plasma concentration all 1028 samples measured with same high-performance liquid chromatography method. Maximum likelihood estimates sought for parameters NONMEM program. best structural covariate-free one-compartment an exponential error account intersubject variability proportional intrasubject variability. apparent clearance found be correlated aspartate transaminase, type disease (malignant or other). volume distribution related body weight. formulation (1% powder form crystal form) (milligrams per kilogram) influenced absorption rate constant. It estimated that expressed kilogram weight is low at early infancy, then increases maximum approximately age and, thereafter, decreases. In conclusion, we have developed children, particularly those younger than 4 old, takes into consideration not only size, but also several other covariates.