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Anti-IL-33 mAbPK / Target EngagementCOPD-focused development

Tozorakimab PK/Target Engagement Simulator

Explore tozorakimab SC and IV dosing, monoclonal antibody exposure, and predicted systemic IL-33/sST2 inhibition using a published population PK/target-engagement framework.

Published model

Sadiq / Yu et al., BJCP 2024

Drug class

Human IgG1 anti-IL-33 monoclonal antibody

Key output

IL-33/sST2 inhibition from baseline

What this tozorakimab simulator models

The simulator combines a two-compartment monoclonal antibody PK model with a mechanistic IL-33 / soluble ST2 binding system. It is built for scientific exploration of exposure and target engagement, not individual clinical dosing.

ComponentPublished value / structureHow to use it
Model structureTwo-compartment mAb PKSC depot or IV input with central and peripheral disposition
ClearanceCL = 0.87 L/dayBase clearance in the published population PK/TE model
DistributionV1 = 12.64 L; V2 = 2.61 L; Q = 0.21 L/dayLarge central volume and slow distribution typical of mAb PK
SC absorptionKa = 0.48 day⁻¹; F = 45%Supports SC dosing scenarios from 30–600 mg
Target engagementIL-33 / soluble ST2 binding systemMechanistic central-compartment turnover and binding model
Clinical contextHealthy volunteers and mild COPDSimulator emphasizes systemic IL-33/sST2 complex inhibition

Simulation scenarios

SC or IV administration

Compare subcutaneous absorption with direct central input

30–600 mg dose range

Explore exposure and target engagement over the studied dose range

Q2W, Q4W, Q6W regimens

Evaluate durability of IL-33/sST2 inhibition across maintenance intervals

Body weight scenario analysis

Optional exploratory allometric scaling; off by default for paper-faithful runs

PK + TE outputs

View total tozorakimab concentration and predicted systemic target engagement

Why it matters

Anti-IL-33 programs are highly dependent on sustained pathway coverage. A PK/TE simulator makes it easier to see how dose, dosing interval, route, and body-size assumptions affect both antibody exposure and downstream systemic target engagement.

Best suited for

  • Clinical pharmacology and DMPK review of anti-cytokine mAb PK
  • Pharmacometrics training around PK/target-engagement models
  • Scenario exploration for Q2W, Q4W, and Q6W regimen durability
  • Understanding how IL-33/sST2 inhibition relates to exposure over time

Frequently asked questions

What is tozorakimab?

Tozorakimab is a human IgG1 monoclonal antibody targeting interleukin-33 (IL-33), studied in healthy volunteers and patients with mild chronic obstructive pulmonary disease.

What does this simulator predict?

The simulator predicts serum tozorakimab concentration-time profiles, last-interval Cmax, trough, AUC, terminal half-life, and systemic IL-33/sST2 target engagement after SC or IV dosing.

Which regimens can be explored?

Users can simulate 30–600 mg doses given every 2, 4, or 6 weeks, with 1–12 doses and optional exploratory body-weight scaling.

Is this for clinical decision-making?

No. The PKPDBuilder simulator is for research, education, and pharmacometric exploration. It is not intended for patient-specific clinical dosing decisions.