Fundamental & clinical pharmacology
-
Fundam Clin Pharmacol · Dec 2008
Clinical TrialIntegration of modelling and simulation into the development of intravenous busulfan in paediatrics: an industrial experience.
Busulfan (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. ⋯ 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.