1. Effect of weight and maturation on busulfan clearance in infants and small children undergoing hematopoietic cell transplantation
- Author
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Robbert G. M. Bredius, Jaap Jan Boelens, Geoff D.E. Cuvelier, Radojka M. Savic, Imke H. Bartelink, Morton J. Cowan, Christopher C. Dvorak, Mary Slatter, Peter J. Shaw, Sung-Yun Pai, Janel Long-Boyle, Luis M. Pereira, Rob Wynn, and Clinical pharmacology and pharmacy
- Subjects
Male ,Pediatrics ,Transplantation Conditioning ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,030226 pharmacology & pharmacy ,0302 clinical medicine ,Child ,Pediatric ,education.field_of_study ,Hematopoietic cell transplantation ,medicine.diagnostic_test ,Area under the curve ,Hematopoietic Stem Cell Transplantation ,Hematology ,Alkylating ,3. Good health ,030220 oncology & carcinogenesis ,Child, Preschool ,Female ,Autologous ,medicine.drug ,medicine.medical_specialty ,Population ,Clinical Sciences ,Immunology ,Antineoplastic Agents ,Transplantation, Autologous ,Article ,03 medical and health sciences ,Pharmacokinetics ,Clinical Research ,medicine ,Humans ,Dosing ,education ,Preschool ,Antineoplastic Agents, Alkylating ,Busulfan ,Retrospective Studies ,Transplantation ,business.industry ,Infant, Newborn ,Infant ,Perinatal Period - Conditions Originating in Perinatal Period ,Newborn ,Surgery ,Good Health and Well Being ,Therapeutic drug monitoring ,business - Abstract
Little information is currently available regarding the pharmacokinetics (PK) of busulfan in infants and small children to help guide decisions for safe and efficacious drug therapy. The objective of this study was to develop an algorithm for individualized dosing of i.v. busulfan in infants and children weighing ≤12 kg, that would achieve targeted exposure with the first dose of busulfan. Population PK modeling was conducted using intensive time-concentration data collected through the routine therapeutic drug monitoring of busulfan in 149 patients from 8 centers. Busulfan PK was well described by a 1-compartment base model with linear elimination. The important clinical covariates affecting busulfan PK were actual body weight and age. Based on our model, the predicted clearance of busulfan increases approximately 1.7-fold between 6 weeks to 2 years of life. For infants age
- Published
- 2013