• L Nguyen.
• Institut de Recherche Pierre Fabre, Castres, France. laurent.nguyen@pierre-fabre.com
• Fundam Clin Pharmacol. 2008 Dec 1; 22 (6): 599-604.

AbstractBusulfan (Bu) is commonly used in preparative conditioning regimen prior to bone marrow transplantation in infants (< 1 year old), children and adolescents (up to 17 years old). The clinical development of an intravenous form of busulfan (Busilvex) was based on pharmacokinetic (PK) modeling and simulation techniques. A retrospective population PK analysis was initially performed from a first study in 24 pediatric patients (0.45-16.7 years old) and a log-linear relationship between body weight and Busilvex clearance was demonstrated with no age-dependency. For an optimal area under the curve (AUC) targeting, a new Bu dosing regimen [i.e. 5 dose levels (0.80 to 1.20 mg/kg) adjusted to 5 discrete weight categories] was developed and assessed through population PK-based simulations. The benefit from this new dosing strategy was validated in a second trial including 55 children (0.30-17.2 years old). This prospective trial confirmed the previous simulations: an efficient therapeutic targeting whatever the patient's age or body weight. Over 80% of the children were within the desired plasma exposure window, and the initial PK model was validated on the confirmatory dataset.

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