Population Pharmacokinetic and Pharmacodynamic Modeling of Pegvisomant in Asian and Western Acromegaly Patients

Pegvisomant is a growth hormone (GH) receptor antagonist that normalizes insulin‐like growth factor I (IGF‐I) levels in patients with acromegaly. Although the dose of pegvisomant is determined by the IGF‐I level, the pharmacokinetic and pharmacodynamic (PK/PD) model for pegvisomant concentration and IGF‐I 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 acromegaly patients, models were developed to characterize the PK/PD of pegvisomant. The PD variables were IGF‐I 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 IGF‐I 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 patients.