Erenumab exposure and immune tolerance in rats

Monomer — no immunosuppression

Conditional typical-input PK and/or immune projection with declared weights, observation inputs and finite calendars.

Readouts

Serum · ug/mL

Serum over the selected simulation window.

Ath · 1/uL

Ath over the selected simulation window.

Atr · 1/uL

Atr over the selected simulation window.

Model ada signal · dimensionless

Model ada signal over the selected simulation window.

Study purpose

• How do the model's key biological readouts change under monomer — no immunosuppression?

Assumptions

• Typical apparent PK supplies a declared immune-model input; individual fitted rat profiles, random effects, occasion effects and residual observations are not reconstructed.
• Observed ADA S/N is a separate input with study cutoff 2 or 1.5. Supplied step profiles are authored controls, not original rat observations; right-continuous interpolation is declared.
• Model-derived ADA does not feed back into clearance. The lag gates current activated-helper values from treatment start without dose-by-dose resets, an extra elimination state or an added assay baseline.
• The supplementary numerical ADA scaling uses alpha 77 nmol/day, K 500 counts/day and N 1000 nmol/uL; this is a declared source scaling convention, not established absolute ADA concentration or assay calibration.
• Erenumab bioavailability is unknown and already absorbed into CL/F and V/F. Apparent central and removed quantities are algebraic dose-equivalent coordinates, not established true systemic drug amounts.
• Study dose conversion uses a fixed assumed 0.280 kg rat. Weight is not a final PK covariate and original time-varying animal weights are unavailable.
• Finite small-molecule depot/systemic equations realize single-dose kernels on explicitly authored calendars. They are separate from a steady-state multiple-dose formula or original individual exposures.
• TAC and MTX use active-moiety mass conventions of 804.02 and 454.44 g/mol; nM equals mg/L times 1e6 divided by molecular weight. Original reagent hydration/salt mass is not inferred.
• Small-molecule removed observers include presystemic unavailable fraction plus systemic elimination. The per-kg coordinates do not require another animal-weight factor.
• TAC concentration represents the combined TAC/SIR helper-proliferation effect; no independent sirolimus concentration coordinate is specified.
• MTX inhibits activated-helper gain while the corresponding naive-helper loss is unchanged, following the printed source equations.
• The chronic fixed calendar extends through day 238 and the displayed horizon through day 364. It is an authored deterministic realization, not a 1000-animal prediction or an exact source event array.
• Drug-free zero activated-cell initials are derived steady-state assumptions; naive baselines are source-supported. Cell counts are dimensionless entities per microliter.
• No rat receptor occupancy, covalent binding, drug-ADA complex, clinical efficacy, calibrated ADA incidence or treatment recommendation is defined.