Population Pharmacokinetics and Pharmacodynamics of Benralizumab in Healthy Volunteers and Patients With Asthma.
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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
Benralizumab is a humanized, afucosylated, 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 YesBindingDetails