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CD11a turnover under fixed efalizumab exposure

Explore CD11a synthesis, free-target degradation and bound-target internalization under a specified constant free-antibody concentration. The concentration is an external input; no antibody PK, dosing history or clinical response is predicted.

Prediction of the Pharmacokinetics, Pharmacodynamics, and Efficacy of a Monoclonal Antibody, Using a Physiologically Based Pharmacokinetic FcRn Model ↗
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No exposure: target equilibrium

How does target turnover preserve its baseline in the absence of antibody exposure? Deterministic exploratory scope.

0–672 hour

Study

No exposure: target equilibrium

How does target turnover preserve its baseline in the absence of antibody exposure? Deterministic exploratory scope.

Readouts

Free cd11a relative to baseline· %
Free target concentration divided by the fixed reference concentration; not receptor occupancy.
Total cd11a relative to baseline· %
Free plus bound target relative to the fixed reference concentration; reference-normalized values are not probabilities.
Quasi steady state bound fraction· %
Binding fraction fixed by the specified driver and half-binding concentration; target turnover changes total target rather than this algebraic fraction.

Study purpose

  • How does target turnover preserve its baseline in the absence of antibody exposure?

Interpretation limits

  • The free-antibody driver is external and constant. The original effect-site matrix and treatment-time exposure histories are unresolved; no antibody PK or dose conversion is executed.
  • Baseline target defines synthesis and normalization, while starting target concentrations are explicitly fixed by each scenario. Changing baseline requires coordinated initial-state admission; it is excluded from independent analysis axes in this draft.
  • The recovery condition begins from a specified depleted target after exposure removal. It is not a continuously simulated treatment/washout history.
  • Complex internalization is interpreted in 1/h for dimensional consistency; the source printed L/h is an unresolved unit conflict.
  • The deterministic log-effect is a fixed sensitivity input. Original variability distributions, full PBPK, populations and target-to-PASI coupling remain incomplete.
  • Control bounds are independently authored exploratory ranges, not observed covariate ranges or clinical exposure recommendations.
  • The initial target and reference target remain fixed by the selected configuration; baseline is not an independent editable control.
  • Free and total target percentages are distinct from the algebraic bound fraction. No clinical efficacy or safety prediction is supported.
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External exposure

Exploratory external input; no PK prediction or dose conversion is implied.

ug/mL
0 → —
Target turnover

Table 1 Kdeg; reported CV10%.

1/hour
0.0185 → —

Table 1 Kint; interpreted first-order rate, printed unit conflict retained.

1/hour
0.1 → —
Target binding

Table 1 Km=(koff+kint)/kon, not the FcRn KD.

umol/L
0.000573 → —
Simulation time
hour
hour
672 → 168

Time between reported samples.

hour
2 → 1

2 changes · Variation 1

Continue in the background and keep the result.

Biology

Explore CD11a synthesis, free-target degradation and bound-target internalization under a specified constant free-antibody concentration. The concentration is an external input; no antibody PK, dosing history or clinical response is predicted.

Explore CD11a synthesis, free-target degradation and bound-target internalization under a specified constant free-antibody concentration. The concentration is an external input; no antibody PK, dosing history or clinical response is predicted.
States & equation dependencies
What are the modeled states and equation-linked processes?Representative technical topology with 5 selected states: Total cd11a, Cumulative complex internalization, Cumulative free target degradation, Elapsed time, Cumulative target synthesis. Displayed equation-linked dependencies: from Total cd11a to Cumulative complex internalization; from Total cd11a to Cumulative free target degradation. There are no displayed entry points. There are no separately labeled equation controls.TECHNICAL TOPOLOGYWhat are the modeled states and equation-linked processes?Selected equation-linked states · model time unit: hourTotal cd11aumol/LCumulative complexinternalizationumol/LCumulative free targetdegradationumol/LElapsed timehourCumulative target synthesisumol/L
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

  • The free-antibody driver is external and constant. The original effect-site matrix and treatment-time exposure histories are unresolved; no antibody PK or dose conversion is executed.
  • Baseline target defines synthesis and normalization, while starting target concentrations are explicitly fixed by each scenario. Changing baseline requires coordinated initial-state admission; it is excluded from independent analysis axes in this draft.
  • The recovery condition begins from a specified depleted target after exposure removal. It is not a continuously simulated treatment/washout history.
  • Complex internalization is interpreted in 1/h for dimensional consistency; the source printed L/h is an unresolved unit conflict.
  • The deterministic log-effect is a fixed sensitivity input. Original variability distributions, full PBPK, populations and target-to-PASI coupling remain incomplete.
  • Control bounds are independently authored exploratory ranges, not observed covariate ranges or clinical exposure recommendations.
  • The initial target and reference target remain fixed by the selected configuration; baseline is not an independent editable control.
  • Free and total target percentages are distinct from the algebraic bound fraction. No clinical efficacy or safety prediction is supported.

Parameter origins

  • Released executable model definition; exact publication locator not reported

Validation & references

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

Prediction of the Pharmacokinetics, Pharmacodynamics, and Efficacy of a Monoclonal Antibody, Using a Physiologically Based Pharmacokinetic FcRn Model ↗

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

Model details

7 parameters · 5 states · 5 equations · 6 derived outputs

Classification & API access
Therapeutic
Efalizumab
Modality
Monoclonal antibody
Target
CD11a, ITGAL
Disease / scope
Psoriasis (source context; no clinical response prediction)
ParameterDefaultUnitDescription
Qss binding constantbinding_half_concentration0.000573umol/LTable 1 Km=(koff+kint)/kon, not the FcRn KD.
Complex internalizationcomplex_internalization0.11/hourTable 1 Kint; interpreted first-order rate, printed unit conflict retained.
Free efalizumab effect site concentrationdriver_ug_ml0ug/mLExploratory external input; no PK prediction or dose conversion is implied.
Individual log degradation effecteta_target_degradation0dimensionlessDeterministic log-multiplier, not a recovered source random-effects distribution.
Drug molecular weightmw_drug148841g/molTable 1 efalizumab molecular weight.
Drug free target baselinetarget_baseline0.01umol/LTable 1 Rmax, estimated by source authors.
Free target degradationtarget_degradation0.01851/hourTable 1 Kdeg; reported CV10%.

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