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

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Citation

Wang B, Yan L, Yao Z, Roskos LK

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

CPT Pharmacometrics Syst Pharmacol. 2017 Apr;6(4):249-257. doi: 10.1002/psp4.12160. Epub 2017 Jan 21.

PubMed ID
28109128 [View in PubMed
]
Abstract

focusylat Benralizumab是人性化的ed, anti-interleukin-5 receptor alpha, immunoglobulin G (IgG) 1 kappa 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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
Drug Target Kind Organism Pharmacological Action Actions
Benralizumab Low affinity immunoglobulin gamma Fc region receptor III-A Protein Humans
Yes
Binding
Details