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Population Pharmacokinetics and Pharmacodynamics of Benralizumab in Healthy Volunteers and Patients With Asthma.

ABSTRACT: Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor ?, immunoglobulin G (IgG) 1 ? monoclonal antibody. We developed a population pharmacokinetic (PK)/pharmacodynamic (PD) model for benralizumab by analyzing PK and blood eosinophil count data from two healthy volunteer studies (N?=?48) and four studies in patients with asthma (N?=?152). Benralizumab PK was dose-proportional and adequately described by a two-compartment model with first-order elimination from the central compartment and first-order absorption from the subcutaneous dosing site. The estimated systemic clearance and volume of distribution were typical for human IgG. Body weight and high-titer antidrug antibodies were identified as relevant covariates influencing the PK of benralizumab. Depletion of blood eosinophil counts was depicted by a modified transit model in which benralizumab induced depletion of eosinophils in each age compartment. Stochastic simulations supported an every-8-week dosing schedule of benralizumab for a phase IIb study in patients with uncontrolled asthma.

SUBMITTER: Wang B 

PROVIDER: S-EPMC5397562 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Population Pharmacokinetics and Pharmacodynamics of Benralizumab in Healthy Volunteers and Patients With Asthma.

Wang B B   Yan L L   Yao Z Z   Roskos L K LK  

CPT: pharmacometrics & systems pharmacology 20170121 4

Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α, immunoglobulin G (IgG) <sub>1</sub> κ monoclonal antibody. We developed a population pharmacokinetic (PK)/pharmacodynamic (PD) model for benralizumab by analyzing PK and blood eosinophil count data from two healthy volunteer studies (N = 48) and four studies in patients with asthma (N = 152). Benralizumab PK was dose-proportional and adequately described by a two-compartment model with first-order elimination from the cent  ...[more]

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