Rik Schoemaker (1), Armel Stockis (2)
(1) SGS Exprimo, (2) UCB Pharma
Objectives: To investigate the adequacy of allometric scaling of adult brivaracetam population pharmacokinetic parameters to a pediatric patient population using either body weight (WT) or lean body weight (LBW).
Methods: A population pharmacokinetic model for brivaracetam (single-compartment, first order absorption and elimination, V and Cl allometrically scaled using WT or LBW with theoretical exponents) was previously developed, using data from 1188 subjects from 2 Phase II and 3 Phase III clinical trials in adult subjects suffering from partial epilepsy and localization-related or generalized epilepsy. A currently on-going trial in pediatric patients (1 month-<2 years, n=30; 2-11 years, n=52; 12-<16 years, n=18) allows a comparison of clearance and volume predictions based on allometric scaling of the adult population parameters with those obtained in the actual pediatric patient population (estimated using NONMEM V7.2.0 with FOCE-I), using the adult structural model restricted to the pediatric patient data.
Results: Empirical Bayes estimates for Cl from the pediatric model were virtually identical whether WT or LBW was used. Individual pediatric Cl estimates were predicted adequately and without bias using the adult parameters with LBW scaling. LBW scaling was superior to WT scaling.
Conclusions: Allometric scaling from adults to pediatric patients using LBW provide superior predictions of pediatric Cl, but pediatric patients on their own are equally well described using WT or LBW scaling. This means pediatric dosing adaptations can be WT-based and do not require the more complex LBW-scaling, and allometric principles can be used to scale brivaracetam pharmacokinetics from adults to children.
Reference: PAGE 22 (2013) Abstr 2674 [www.page-meeting.org/?abstract=2674]
Poster: Paediatrics