Population pharmacokinetic and pharmacodynamic modeling of pegvisomant in asian and Western XXXX @entity1 .

@entity1 @entity2012 @entity442 @entity9045
Pegvisomant is a @entity9045 antagonist that normalizes @entity442 ( @entity442 ) levels in @entity1 with @entity2012 . Although the dose of pegvisomant is determined by the @entity442 level, the pharmacokinetic and pharmacodynamic (PK/PD) model for pegvisomant concentration and @entity442 reduction has not been established. This study was conducted to characterize PK/PD of pegvisomant, and to determine the influence of covariates on the pegvisomant PK/PD. Based on the data from 5 phase III studies in 168 @entity2012 @entity1 , models were developed to characterize the PK/PD of pegvisomant. The PD variables were @entity442 serum concentrations. The modeling was performed with a nonlinear mixed-effects approach using NONMEM. After subcutaneous dosing, the PK of pegvisomant was described by a steady state PK model with dose- dependent clearance. Baseline GH and age were significant covariates for the clearance. A sigmoid E(max) model adequately described the relationship between @entity442 and pegvisomant concentrations. Baseline GH was found to be a significant covariate for the baseline effect (E(0)) and IC(50). The PK/PD properties of pegvisomant were not significantly different between Asian and Western @entity1 .
