title: Population Pharmacokinetics and Pharmacodynamics of Benralizumab in Healthy Volunteers and Patients With Asthma.
abstract: Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α, immunoglobulin G (IgG)1κ 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.
authors.affiliation: MedImmune LLC, Mountain View, California, USA.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: MedImmune LLC, Mountain View, California, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yan
authors.affiliation: MedImmune LLC, Mountain View, California, USA.|Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yao
authors.affiliation: MedImmune LLC, Gaithersburg, Maryland, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Roskos
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013269:Stochastic Processes; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; C571386:benralizumab