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AZD7442 total-antibody pharmacokinetics

Two-compartment total-serum PK with explicit IM/IV administration, fixed covariates and empirical input-weighted amount accounting.

Accelerating therapeutics development during a pandemic: population pharmacokinetics of the long-acting antibody combination AZD7442 (tixagevimab/cilgavimab) in the prophylaxis and treatment of COVID-19 ↗

Antimicrobial Agents and Chemotherapy

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MODEL IN MOTION 18 sec

How does body weight alter the combination exposure profile?

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fig4 typical 600mg gluteal azd7442

Conditional fixed-covariate total-serum PK following the specified explicit administrations.

0–1,000 day

Scenario details

fig4 typical 600mg gluteal azd7442

Conditional fixed-covariate total-serum PK following the specified explicit administrations.

Readouts

Central conc · ug/mL
Central conc over the selected simulation window.
Exposure (AUC) · ug*day/mL
Exposure (AUC) over the selected simulation window.
Cavg cum · ug/mL
Cavg cum over the selected simulation window.

Study purpose

  • How do the model's key biological readouts change under fig4 typical 600mg gluteal azd7442?

Assumptions

  • The analyte is total AZD7442 serum concentration. The model does not calculate separate component trajectories or antibody binding or clinical response.
  • Covariates remain fixed within each condition. Their empirical associations do not establish causal mechanisms.
  • The IM/site factor scales model exposure input and may exceed one. Its apparent input-weighted ledger differs from nominal administered mass.
  • Three amount states describe depot, central and peripheral PK. AUC and elapsed time are nonfeedback observers.
  • The current amount and CL-times-AUC readouts use fixed context coefficients. The input-weighted ledger weights the depot by the same empirical IM factor.
  • Each administration explicitly targets depot or central amount. The selected condition fixes the initial values, coefficients and administration history.
  • No original cohort fit, random-effect sampling, observation-noise simulation, individual dose advice or clinical efficacy prediction is provided.

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1000 → 168

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Biology

Two-compartment total-serum PK with explicit IM/IV administration, fixed covariates and empirical input-weighted amount accounting.

Two-compartment total-serum PK with explicit IM/IV administration, fixed covariates and empirical input-weighted amount accounting.

Model details

21 parameters · 5 states · 5 equations · 18 derived outputs

Classification & API access
Therapeutic
AZD7442 (total-antibody analyte)
Modality
Monoclonal antibody
Target
SARS-CoV-2 Spike RBD
Disease / scope
SARS-CoV-2 pre-exposure prophylaxis
ParameterDefaultUnitDescription
Beta clearance diabetesbeta_cl_diabetes0.198—Fixed coefficient or covariate for the selected total-serum PK context.
Beta fim thighbeta_fim_thigh0.416—Fixed coefficient or covariate for the selected total-serum PK context.
Beta absorption rate age OVER65beta_ka_age_over65-0.325—Fixed coefficient or covariate for the selected total-serum PK context.
Beta absorption rate bmi GE30beta_ka_bmi_ge30-0.254—Fixed coefficient or covariate for the selected total-serum PK context.
Beta absorption rate diabetesbeta_ka_diabetes-0.318—Fixed coefficient or covariate for the selected total-serum PK context.
Beta absorption rate malebeta_ka_male0.543—Fixed coefficient or covariate for the selected total-serum PK context.
Beta central distribution volume blackbeta_vc_black-0.251—Fixed coefficient or covariate for the selected total-serum PK context.
Body weightbody_weight_kg80.6kgFixed coefficient or covariate for the selected total-serum PK context.
Systemic clearancecl_l_day0.0504L/dayFixed coefficient or covariate for the selected total-serum PK context.
Intramuscular bioavailability fractionfim_fraction0.671—Fixed coefficient or covariate for the selected total-serum PK context.
Has diabeteshas_diabetes0—Fixed coefficient or covariate for the selected total-serum PK context.
Is age OVER65is_age_over650—Fixed coefficient or covariate for the selected total-serum PK context.
Is black raceis_black_race0—Fixed coefficient or covariate for the selected total-serum PK context.
Is bmi GE30is_bmi_ge300—Fixed coefficient or covariate for the selected total-serum PK context.
Is maleis_male1—Fixed coefficient or covariate for the selected total-serum PK context.
Is thigh injectionis_thigh_injection0—Fixed coefficient or covariate for the selected total-serum PK context.
Absorption rate constantka_1_day0.111/dayFixed coefficient or covariate for the selected total-serum PK context.
Intercompartmental clearanceq_l_day0.395L/dayFixed coefficient or covariate for the selected total-serum PK context.
Reference weightreference_weight_kg70kgFixed coefficient or covariate for the selected total-serum PK context.
Central distribution volumevc_l3.36LFixed coefficient or covariate for the selected total-serum PK context.
Peripheral distribution volumevp_l1.83LFixed coefficient or covariate for the selected total-serum PK context.

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