891 Population Pharmacokinetics Analysis of Motavizumab in Children at Risk for Respiratory Syncytial Virus Infection

Abstract

Aims: To develop a population pharmacokinetics (PK) model and evaluate the impact of demographic covariates on PK of motavizumab in young children. Methods: Motavizumab serum concentrations from 6 pediatric (n=4316) studies and an adult study (n=30) were modeled simultaneously using nonlinear mixed-effects modeling. Children ≤24 months received up to 5 monthly doses of motavizumab 3 or 15 mg/kg. The structural PK model with different random effect assignments was evaluated first followed by assessment of effect of chronologic age (CA), gestational age (GA), body weight (BW), sex, race, and presence of CLD on motavizumab clearance (CL) and volume of distribution (V2) using NONMEM.. Results: Motavizumab serum PK best fit a twocompartment model; CL and V2 increased with BW. CL and V2 were related to the sum of GA and CA and were described using an asymptoticexponential model. Covariate analysis identified 7% lower motavizumab serum CL in infants without CLD compared with infants with CLD. V2 was 23% lower in Hispanic infants compared with other races. After accounting for demographic covariates, there was 25% inter-individual variability in CL and 23% residual variability in motavizumab concentrations. Conclusions: Population PK analysis of motavizumab concentrations demonstrated increased clearance with CA and BW. Motavizumab serum concentrations were similar across a range of GA, CA and BW confirming appropriateness of BWbased dosing. Given the inter-individual variability in motavizumab concentrations, the marginally lower clearance in patients without CLD and slightly lower volume of distribution in Hispanic patients are not expected to be clinically significant. Sponsored by MedImmune.