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Healthy-adult antibody exposure and complement suppression

Explore two-compartment serum antibody exposure after a fixed intravenous infusion and an empirical concentration-dependent terminal complement activity readout. This independent healthy-adult fit uses body weight for disposition and measured baseline complement activity for the half-inhibitory concentration.

Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12 (proposed eculizumab biosimilar) and reference eculizumab ↗

European Journal of Clinical Pharmacology

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Lower adult body-weight context

How does lower adult body weight change exposure and complement suppression after a fixed infusion? Fixed-effect healthy-adult exploration; no simulated population interval.

0–1,512 hour

Study

Lower adult body-weight context

How does lower adult body weight change exposure and complement suppression after a fixed infusion? Fixed-effect healthy-adult exploration; no simulated population interval.

Readouts

Central serum antibody concentration· ug/mL
Central amount divided by central volume. SB12 and reference antibody share this fixed-effect representation.
Terminal complement activity· %
Empirical concentration-inhibition serum assay readout. Measured baseline covariate modifies IC50, while fitted E0 sets drug-free activity.
Exposure (AUC)· ug*h/mL
Central concentration integral since simulation start; specify an interval before interpreting AUCtau.

Study purpose

  • How does lower adult body weight change exposure and complement suppression after a fixed infusion?

Interpretation limits

  • Deterministic healthy-adult fixed effects; this independent fit is distinct from the pooled healthy/patient model.
  • The measured baseline complement covariate adjusts IC50; it does not set the simulated zero-drug activity. Fitted E0 supplies that intercept.
  • The complement readout is an empirical serum assay percentage, not molecular C5 occupancy, a probability or an efficacy/safety endpoint.
  • Body weight changes clearance and central volume under a fixed 300 mg dose; these scenarios are not mg/kg regimens.
  • Cumulative exposure integrates from the chosen simulation start; it is not automatically an interval AUCtau.
  • Original individuals, between-subject variability, residual sampling, pcVPC and bootstrap are not reproduced. No patient LDH model or clinical dose recommendation applies.
  • Synthetic baseline-covariate and zero-dose controls are private diagnostics, not observed subjects or paper figure reproduction.
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PK distribution

Fixed adult body weight (kg); alters disposition under an unchanged fixed mg infusion.

kg

Suggested: 35–105. You can explore beyond this range.

70 → —
Complement readout

Measured baseline serum terminal complement activity covariate (%). Adjusts effective IC50 only; fitted E0 sets the drug-free readout.

%

Suggested: 43.88–131.6. You can explore beyond this range.

87.75 → —

pd ic50 ug ml. Fixed-effect parameter of the independent healthy-adult model.

ug/mL

Suggested: 18.1–54.3. You can explore beyond this range.

36.2 → —

Fitted drug-free terminal complement activity intercept (%), distinct from the measured baseline activity covariate.

%

Suggested: 43.1–129.3. You can explore beyond this range.

86.2 → —
PK clearance

pk cl l h. Fixed-effect parameter of the independent healthy-adult model.

L/h

Suggested: 0.00885–0.02655. You can explore beyond this range.

0.0177 → —
Simulation time
hour
hour
1512 → 168

Time between reported samples.

hour
12 → 1

2 changes · Variation 1

Continue in the background and keep the result.

Biology

Explore two-compartment serum antibody exposure after a fixed intravenous infusion and an empirical concentration-dependent terminal complement activity readout. This independent healthy-adult fit uses body weight for disposition and measured baseline complement activity for the half-inhibitory concentration.

Explore two-compartment serum antibody exposure after a fixed intravenous infusion and an empirical concentration-dependent terminal complement activity readout. This independent healthy-adult fit uses body weight for disposition and measured baseline complement activity for the half-inhibitory concentration.
States & equation dependencies
What are the modeled states and equation-linked processes?Representative technical topology with 4 selected states: Central-compartment drug amount, Peripheral-compartment drug amount, Exposure (AUC), Elapsed. Displayed equation-linked dependencies: between Peripheral-compartment drug amount and Central-compartment drug amount; from Central-compartment drug amount to Exposure (AUC). Displayed model or scenario entry points: Administered input enters Central-compartment drug amount. There are no separately labeled equation controls.TECHNICAL TOPOLOGYWhat are the modeled states and equation-linked processes?Selected equation-linked states · model time unit: hourAdministered inputCentral-compartment drugamountmgPeripheral-compartment drugamountmgExposure (AUC)ug*h/mLElapsedh
Teal arrows show relationships between modeled states and do not always represent material transfer. Peach arrows mark administered or scenario-defined entry points.

Assumptions & evidence

Assumptions & limitations

  • Deterministic healthy-adult fixed effects; this independent fit is distinct from the pooled healthy/patient model.
  • The measured baseline complement covariate adjusts IC50; it does not set the simulated zero-drug activity. Fitted E0 supplies that intercept.
  • The complement readout is an empirical serum assay percentage, not molecular C5 occupancy, a probability or an efficacy/safety endpoint.
  • Body weight changes clearance and central volume under a fixed 300 mg dose; these scenarios are not mg/kg regimens.
  • Cumulative exposure integrates from the chosen simulation start; it is not automatically an interval AUCtau.
  • Original individuals, between-subject variability, residual sampling, pcVPC and bootstrap are not reproduced. No patient LDH model or clinical dose recommendation applies.
  • Synthetic baseline-covariate and zero-dose controls are private diagnostics, not observed subjects or paper figure reproduction.

Parameter origins

  • Lee 2024 Supplement Tables A1/A2

Validation & references

One or more implementation checks are available; this is not a claim of full model reproduction.

Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12 (proposed eculizumab biosimilar) and reference eculizumab ↗

Available reference curves can be added to the plot when their scenario, readout, time and units match.

Model details

15 parameters · 4 states · 4 equations · 26 derived outputs

Classification & API access
Therapeutic
Eculizumab, SB12
Modality
Monoclonal antibody
Target
Complement C5
Disease / scope
Healthy adults
ParameterDefaultUnitDescription
Baseline IC50 exponentbaseline_ic50_exponent0.14dimensionlessbaseline ic50 exponent. Fixed-effect parameter of the independent healthy-adult model.
Baseline tca pctbaseline_tca_pct87.75%Measured baseline serum terminal complement activity covariate (%). Adjusts effective IC50 only; fitted E0 sets the drug-free readout.
Baseline tca reference pctbaseline_tca_ref_pct87.75%baseline tca ref pct. Fixed-effect parameter of the independent healthy-adult model.
Body weightbody_weight_kg82.4kgFixed adult body weight (kg); alters disposition under an unchanged fixed mg infusion.
PD E0 healthy pctpd_e0_healthy_pct86.2%Fitted drug-free terminal complement activity intercept (%), distinct from the measured baseline activity covariate.
PD hillpd_hill4.52dimensionlesspd hill. Fixed-effect parameter of the independent healthy-adult model.
PD IC50pd_ic50_ug_ml36.2ug/mLpd ic50 ug ml. Fixed-effect parameter of the independent healthy-adult model.
PD Imax healthy fractionpd_imax_healthy_fraction0.931pd imax healthy fraction. Fixed-effect parameter of the independent healthy-adult model.
PK clearancepk_cl_l_h0.0177L/hpk cl l h. Fixed-effect parameter of the independent healthy-adult model.
PK clearance weight exponentpk_cl_weight_exponent0.763dimensionlesspk cl weight exponent. Fixed-effect parameter of the independent healthy-adult model.
PK intercompartmental clearancepk_q_l_h0.0136L/hpk q l h. Fixed-effect parameter of the independent healthy-adult model.
Central distribution volume — healthy participantspk_vc_healthy_l3.5Lpk vc healthy l. Fixed-effect parameter of the independent healthy-adult model.
PK central distribution volume weight exponentpk_vc_weight_exponent0.684dimensionlesspk vc weight exponent. Fixed-effect parameter of the independent healthy-adult model.
PK peripheral distribution volumepk_vp_l0.785Lpk vp l. Fixed-effect parameter of the independent healthy-adult model.
PK weight referencepk_weight_ref_kg82.4kgpk weight ref kg. Fixed-effect parameter of the independent healthy-adult model.

Related models

Eculizumab and SB12 population PK

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